AJP: Heart and Circulatory Physiology
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An adaptive transfer function for deriving the aortic pressure waveform from a peripheral artery pressure waveform
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We developed a new technique to mathematically transform a peripheral artery pressure (PAP) waveform distorted by wave reflections into the physiologically more relevant aortic pressure (AP) waveform. First, a transfer function relating PAP to AP is defined in terms of the unknown parameters of a parallel tube model of pressure and flow in the arterial tree. The parameters are then estimated from the measured PAP waveform along with a one-time measurement of the wave propagation delay time between the aorta and peripheral artery measurement site (which may be accomplished noninvasively) by exploiting preknowledge of aortic...
Source: AJP: Heart and Circulatory Physiology - October 26, 2009 Category: Cardiology Authors: Swamy, G., Xu, D., Olivier, N. B., Mukkamala, R. Tags: INNOVATIVE METHODOLOGY Source Type: journals
Extraction of morphometry and branching angles of porcine coronary arterial tree from CT imagesEmail this article to a colleague.
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The morphometry (diameters, length, and angles) of coronary arteries is related to their function. A simple, easy, and accurate image-based method to seamlessly extract the morphometry for coronary arteries is of significant value for understanding the structure-function relation. Here, the morphometry of large (≥1 mm in diameter) coronary arteries was extracted from computed tomography (CT) images using a recently validated segmentation algorithm. The coronary arteries of seven pigs were filled with Microfil, and the cast hearts were imaged with CT. The centerlines of the extracted vessels, the vessel radii, and the ve...
Source: AJP: Heart and Circulatory Physiology - October 26, 2009 Category: Cardiology Authors: Wischgoll, T., Choy, J. S., Kassab, G. S. Tags: INNOVATIVE METHODOLOGY Source Type: journals
A random cycle length approach for assessment of myocardial contraction in isolated rabbit myocardiumEmail this article to a colleague.
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It is well known that the strength of cardiac contraction is dependent on the cycle length, evidenced by the force-frequency relationship (FFR) and the existence of postrest potentiation (PRP). Because the contractile strength of the steady-state FFR and force-interval relationship involve instant intrinsic responses to cycle length as well as slower acting components such as posttranslational modification-based mechanisms, it remains unclear how cycle length intrinsically affects cardiac contraction and relaxation. To dissect the impact of cycle length changes from slower acting signaling components associated with persis...
Source: AJP: Heart and Circulatory Physiology - October 26, 2009 Category: Cardiology Authors: Varian, K. D., Xu, Y., Torres, C. A. A., Monasky, M. M., Janssen, P. M. L. Tags: INNOVATIVE METHODOLOGY Source Type: journals
siRNA-mediated knockdown of h-caldesmon in vascular smooth muscleEmail this article to a colleague.
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Smooth muscle contraction involves phosphorylation of the regulatory myosin light chain. However, this thick-filament system of regulation cannot account for all aspects of a smooth muscle contraction. An alternate site of contractile regulation may be in the thin-filament-associated proteins, in particular caldesmon. Caldesmon has been proposed to be an inhibitory protein that acts either as a brake to stop any increase in resting or basal tone, or as a modulatory protein during contraction. The goal of this study was to use short interfering RNA technology to decrease the levels of the smooth muscle-specific isoform of c...
Source: AJP: Heart and Circulatory Physiology - October 26, 2009 Category: Cardiology Authors: Smolock, E. M., Trappanese, D. M., Chang, S., Wang, T., Titchenell, P., Moreland, R. S. Tags: ARTICLES Source Type: journals
Ranolazine, an antianginal agent, markedly reduces ventricular arrhythmias induced by ischemia and ischemia-reperfusionEmail this article to a colleague.
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We tested the effect of the antianginal agent ranolazine on ventricular arrhythmias in an ischemic model using two protocols. In protocol 1, anesthetized rats received either vehicle or ranolazine (10 mg/kg, iv bolus) and were subjected to 5 min of left coronary artery (LCA) occlusion and 5 min of reperfusion with electrocardiogram and blood pressure monitoring. In protocol 2, rats received either vehicle or three doses of ranolazine (iv bolus followed by infusion) and 20 min of LCA occlusion. With protocol 1, ventricular tachycardia (VT) occurred in 9/12 (75%) vehicle-treated rats and 1/11 (9%) ranolazine-treated rats dur...
Source: AJP: Heart and Circulatory Physiology - October 26, 2009 Category: Cardiology Authors: Dhalla, A. K., Wang, W.-Q., Dow, J., Shryock, J. C., Belardinelli, L., Bhandari, A., Kloner, R. A. Tags: ARTICLES Source Type: journals
Pyruvate-fortified cardioplegia evokes myocardial erythropoietin signaling in swine undergoing cardiopulmonary bypassEmail this article to a colleague.
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This study tested the hypothesis that pyruvate-enriched cardioplegia evoked EPO expression and mobilized EPO signaling mechanisms in myocardium. Hearts of pigs maintained on CPB were arrested for 60 min with 4:1 blood-crystalloid cardioplegia. The crystalloid component contained 188 mM glucose ± 24 mM pyruvate. After 30-min cardiac reperfusion with cardioplegia-free blood, the pigs were weaned from CPB. Left ventricular myocardium was sampled 4 h after CPB for immunoblot assessment of HIF-1, EPO and its receptor, the signaling kinases Akt and ERK, and endothelial nitric oxide synthase (eNOS), an effector of EPO sign...
Source: AJP: Heart and Circulatory Physiology - October 26, 2009 Category: Cardiology Authors: Ryou, M.-G., Flaherty, D. C., Hoxha, B., Sun, J., Gurji, H., Rodriguez, S., Bell, G., Olivencia-Yurvati, A. H., Mallet, R. T. Tags: ARTICLES Source Type: journals
Endogenous regulation of cardiovascular function by apelin-APJEmail this article to a colleague.
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Studies have shown significant cardiovascular effects of exogenous apelin administration, including the potent activation of cardiac contraction. However, the role of the endogenous apelin-APJ pathway is less clear. To study the loss of endogenous apelin-APJ signaling, we generated mice lacking either the ligand (apelin) or the receptor (APJ). Apelin-deficient mice were viable, fertile, and showed normal development. In contrast, APJ-deficient mice were not born in the expected Mendelian ratio, and many showed cardiovascular developmental defects. Under basal conditions, both apelin and APJ null mice that survived to adult...
Source: AJP: Heart and Circulatory Physiology - October 26, 2009 Category: Cardiology Authors: Charo, D. N., Ho, M., Fajardo, G., Kawana, M., Kundu, R. K., Sheikh, A. Y., Finsterbach, T. P., Leeper, N. J., Ernst, K. V., Chen, M. M., Ho, Y. D., Chun, H. J., Bernstein, D., Ashley, E. A., Quertermous, T. Tags: ARTICLES Source Type: journals
Additive beneficial effects of lactotripeptides and aerobic exercise on arterial compliance in postmenopausal womenEmail this article to a colleague.
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Central arterial compliance plays an important role in the functional abilities of the vasculature. Two active tripeptides, valine-proline-proline and isoleucine-proline-proline, were isolated from sour milk and were referred to as lactotripeptides (LTP). Because LTP appears to act as an angiotensin-converting enzyme inhibitor, it is plausible to hypothesize that LTP improves arterial compliance. We determined the effects of LTP ingestion alone or in combination with regular aerobic exercise on arterial compliance. A total of 55 postmenopausal women (50–65 yr old) were randomly divided into four groups: placebo, LTP,...
Source: AJP: Heart and Circulatory Physiology - October 26, 2009 Category: Cardiology Authors: Yoshizawa, M., Maeda, S., Miyaki, A., Misono, M., Choi, Y., Shimojo, N., Ajisaka, R., Tanaka, H. Tags: ARTICLES Source Type: journals
Angiotensin II effects on ischemic focal ventricular tachycardia are predominantly mediated through myocardial AT2 receptorEmail this article to a colleague.
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Ischemic focal ventricular tachycardia (VT) occurs in animals and humans. Angiotensin-converting enzyme inhibitors and receptor blockers reduce sudden death in patients with ischemic heart disease. In our dog model of coronary artery occlusion (CAO), we tested the hypothesis that angiotensin II (AGII) will selectively promote focal VT and that the specific AT2 blocker PD-123319 (PD), or AT1 blocker losartan, will affect this VT. Anesthetized dogs (n = 90) underwent CAO, followed by three-dimensional activation mapping of inducible VT. Dogs without VT in 1–3 h after CAO received AGII, and those with VT received either...
Source: AJP: Heart and Circulatory Physiology - October 26, 2009 Category: Cardiology Authors: Gopinathannair, R., Chaudhary, A. K., Xing, D., Ely, D., Zheng, W., Martins, J. B. Tags: ARTICLES Source Type: journals
Altered reactivity to norepinephrine through COX-2 induction by vascular injury in hypercholesterolemic rabbitsEmail this article to a colleague.
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Although long-term use of cyclooxygenase (COX)-2 inhibitors may be associated with increased cardiovascular risk, their effects on vascular reactivity in atherosclerosis has remained largely unexplored. The aim of the present study was to evaluate the role of COX-2 induced by an atherosclerotic process, in the local control of vascular tone. New Zealand White rabbits were fed 0.3% cholesterol and subjected to balloon injury of the abdominal aorta. After 2 wk, the aorta was removed and used for organ bath experiments and immunohistochemistry, and the prostaglandins released were measured using enzyme immunoassays. Hyperchol...
Source: AJP: Heart and Circulatory Physiology - October 26, 2009 Category: Cardiology Authors: Foudi, N., Norel, X., Rienzo, M., Louedec, L., Brink, C., Michel, J.-B., Back, M. Tags: ARTICLES Source Type: journals
Resveratrol attenuates mitochondrial oxidative stress in coronary arterial endothelial cellsEmail this article to a colleague.
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The production of hyperglycemia-induced mitochondrial reactive oxygen species (mtROS) is a key event in the development of diabetic complications. Because resveratrol, a naturally occurring polyphenol, has been reported to confer vasoprotection, improving endothelial function and preventing complications of diabetes, we investigated the effect of resveratrol on mtROS production in cultured human coronary arterial endothelial cells (CAECs). The measurement of MitoSox fluorescence showed that resveratrol attenuates both steady-state and high glucose (30 mM)-induced mtROS production in CAECs, an effect that was prevented by t...
Source: AJP: Heart and Circulatory Physiology - October 26, 2009 Category: Cardiology Authors: Ungvari, Z., Labinskyy, N., Mukhopadhyay, P., Pinto, J. T., Bagi, Z., Ballabh, P., Zhang, C., Pacher, P., Csiszar, A. Tags: ARTICLES Source Type: journals
Antioxidants and aging: NMR-based evidence of improved skeletal muscle perfusion and energeticsEmail this article to a colleague.
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We sought to examine the potential role of oxidative stress on skeletal muscle function with advancing age. Nuclear magnetic resonance (NMR) was employed to simultaneously assess muscle perfusion (arterial spin labeling) and energetics (31P NMR spectroscopy) in the lower leg of young (26 ± 5 yr, n = 6) and older (70 ± 5 yr, n = 6) healthy volunteers following the consumption of either placebo (PL) or an oral antioxidant (AO) cocktail (vitamins C and E and -lipoic acid), previously documented to decrease plasma free radical concentration. NMR measurements were made during and after 5 min of moderate intensity ...
Source: AJP: Heart and Circulatory Physiology - October 26, 2009 Category: Cardiology Authors: Wray, D. W., Nishiyama, S. K., Monnet, A., Wary, C., Duteil, S. S., Carlier, P. G., Richardson, R. S. Tags: ARTICLES Source Type: journals
Pharmacological modifications of the stretch-induced effects on ventricular fibrillation in perfused rabbit heartsEmail this article to a colleague.
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In conclusion, the electrophysiological effects responsible for stretch-induced VF acceleration in the rabbit heart are reduced by the Na+/Ca2+ exchanger blocker KB-R7943 and by propranolol but not by the adenosine A2 receptor antagonist SCH-58261. (Source: AJP: Heart and Circulatory Physiology)
Source: AJP: Heart and Circulatory Physiology - October 26, 2009 Category: Cardiology Authors: Chorro, F. J., Trapero, I., Such-Miquel, L., Pelechano, F., Mainar, L., Canoves, J., Tormos, A., Alberola, A., Hove-Madsen, L., Cinca, J., Such, L. Tags: ARTICLES Source Type: journals
Myocardial ischemia and reperfusion injury is dependent on both IgM and mannose-binding lectinEmail this article to a colleague.
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Complement activation has been shown to play an important role in the inflammation and tissue injury following myocardial ischemia and reperfusion (MI/R). Several recent studies from our laboratory demonstrated the importance of mannose-binding lectin (MBL) as the initiation pathway for complement activation and the resulting pathological effects following MI/R. However, other studies from the past suggest an important role of the classical pathway and perhaps natural antibodies. In the present study, we used newly generated genetically modified mice that lack secreted IgM (sIgM), MBL-A, and MBL-C (sIgM/MBL null) in a plas...
Source: AJP: Heart and Circulatory Physiology - October 26, 2009 Category: Cardiology Authors: Busche, M. N., Pavlov, V., Takahashi, K., Stahl, G. L. Tags: ARTICLES Source Type: journals
Lack of cardiac fibrosis in a new model of high prorenin hyperaldosteronismEmail this article to a colleague.
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The aim of the present study was to test the hypothesis that elevation of prorenin in plasma is sufficient to induce cardiac fibrosis. Normotensive cyp1a1ren-2 transgenic rats with normal plasma prorenin and aldosterone levels were given 0.125% indole-3-carbinol (I3C) orally for a period of 12 wk. Plasma prorenin and aldosterone levels were determined in 4-wk intervals, and cardiac marker enzymes for hypertrophy, fibrosis, and oxidative stress as well as cardiac pathology were investigated. In I3C-treated cyp1a1 ren-2 transgenic rats, plasma prorenin concentrations were >100-fold elevated (≥7.1 ± 2.6 µg ...
Source: AJP: Heart and Circulatory Physiology - October 26, 2009 Category: Cardiology Authors: Peters, J., Schluter, T., Riegel, T., Peters, B. S., Beineke, A., Maschke, U., Hosten, N., Mullins, J. J., Rettig, R. Tags: ARTICLES Source Type: journals
Angiotensin II enhances GABAB receptor-mediated responses and expression in nucleus tractus solitarii of ratsEmail this article to a colleague.
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Angiotensin II (ANG II) increases GABAB receptor expression in neuronal cultures from the nucleus tractus solitarii (NTS). In the present study, the chronic effects of ANG II on GABAB receptor expression and activity were examined in the NTS of Sprague-Dawley rats. Intracerebroventricular infusion of ANG II caused a significant elevation in blood pressure (BP) and an increase in GABAB receptor expression in the NTS. Conversely, chronic NG-nitro-l-arginine methyl ester (l-NAME) treatment also increased BP, but had no effect on GABAB receptor expression in the NTS. Next, we examined the BP response to the GABAB receptor agon...
Source: AJP: Heart and Circulatory Physiology - October 26, 2009 Category: Cardiology Authors: Zhang, Q., Yao, F., O'Rourke, S. T., Qian, S. Y., Sun, C. Tags: ARTICLES Source Type: journals
eNOS uncoupling and endothelial dysfunction in aged vesselsEmail this article to a colleague.
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Endothelial nitric oxide synthase (eNOS) uncoupling is a mechanism that leads to endothelial dysfunction. Previously, we reported that shear stress-induced release of nitric oxide in vessels of aged rats was significantly reduced and was accompanied by increased production of superoxide (18, 27). In the present study, we investigated the influence of aging on eNOS uncoupling. Mesenteric arteries were isolated from young (3 mo) and aged (24 mo) C57 BL/6J mice. The expression of eNOS protein in young vs. aged mice was not significantly different. However, the aged mice had remarkable increases in the ratio of eNOS monomers t...
Source: AJP: Heart and Circulatory Physiology - October 26, 2009 Category: Cardiology Authors: Yang, Y.-M., Huang, A., Kaley, G., Sun, D. Tags: ARTICLES Source Type: journals
Cav1.2 splice variant with exon 9* is critical for regulation of cerebral artery diameterEmail this article to a colleague.
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L-type voltage-dependent Ca2+ channels (VDCCs) are essential for numerous processes in the cardiovascular and nervous systems. Alternative splicing modulates proteomic composition of Cav1.2 to generate functional variation between channel isoforms. Here, we describe expression and function of Cav1.2 channels containing alternatively spliced exon 9* in cerebral artery myocytes. RT-PCR showed expression of Cav1.2 splice variants both containing (1C9/9*/10) and lacking (1C9/10) exon 9* in intact rabbit and human cerebral arteries. With the use of laser capture microdissection and RT-PCR, expression of mRNA for both 1C9/9*/10 ...
Source: AJP: Heart and Circulatory Physiology - October 26, 2009 Category: Cardiology Authors: Nystoriak, M. A., Murakami, K., Penar, P. L., Wellman, G. C. Tags: ARTICLES Source Type: journals
Genetic inhibition of calcineurin induces diastolic dysfunction in mice with chronic pressure overloadEmail this article to a colleague.
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Calcineurin is a Ca2+/calmodulin-dependent protein phosphatase that induces myocardial growth in response to several physiological and pathological stimuli. Calcineurin inhibition, induced either via cyclosporine or genetically, can decrease myocardial hypertrophy secondary to pressure overload without affecting left ventricular (LV) systolic function. Since hypertrophy can also affect LV diastolic function, the goal of this study was to examine the effects of chronic pressure overload (2 wk aortic banding) in transgenic (Tg) mice overexpressing Zaki-4β (TgZ), a specific endogenous inhibitor of calcineurin, on LV dias...
Source: AJP: Heart and Circulatory Physiology - October 26, 2009 Category: Cardiology Authors: Gelpi, R. J., Gao, S., Zhai, P., Yan, L., Hong, C., Danridge, L. M. A., Ge, H., Maejima, Y., Donato, M., Yokota, M., Molkentin, J. D., Vatner, D. E., Vatner, S. F., Sadoshima, J. Tags: ARTICLES Source Type: journals
Activation of a novel estrogen receptor, GPER, is cardioprotective in male and female ratsEmail this article to a colleague.
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Premenopausal females have a lower incidence of cardiovascular disease than their male counterparts, but the mechanism is unclear. Estrogen has been thought to signal through two nuclear receptors: estrogen receptor- or estrogen receptor-β; however, a third, membrane-bound receptor G protein-coupled estrogen receptor (GPER), has been identified and shown to bind estrogen with high affinity. To date, there is little information on GPER in the heart and no study has looked at the effect of GPER activation during myocardial ischemia-reperfusion (I/R). Therefore, the goal of this study was to determine whether activation ...
Source: AJP: Heart and Circulatory Physiology - October 26, 2009 Category: Cardiology Authors: Deschamps, A. M., Murphy, E. Tags: ARTICLES Source Type: journals
Effects of acute and chronic endurance exercise on intracellular nitric oxide in putative endothelial progenitor cells: role of NAPDH oxidaseEmail this article to a colleague.
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We sought to delineate the effects of acute and chronic exercise on the regulation of intracellular nitric oxide (NOi) production in putative endothelial progenitor cells (EPCs). Putative EPC colony-forming units (CFU-EC) were cultured from blood drawn before and after 30 min of treadmill exercise at 75% of maximal oxygen uptake in active (n = 8) and inactive (n = 8) men. CFU-EC were similar between groups at baseline, but increased after exercise in active men only (P = 0.04). CFU-EC expressed lower NADPH oxidase subunit gp91phox mRNA and elevated endothelial nitric oxide synthase mRNA in active relative to inactive men a...
Source: AJP: Heart and Circulatory Physiology - October 26, 2009 Category: Cardiology Authors: Jenkins, N. T., Witkowski, S., Spangenburg, E. E., Hagberg, J. M. Tags: ARTICLES Source Type: journals
Reflex vasoconstriction in aged human skin increasingly relies on Rho kinase-dependent mechanisms during whole body coolingEmail this article to a colleague.
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Primary human aging may be associated with augmented Rho kinase (ROCK)-mediated contraction of vascular smooth muscle and ROCK-mediated inhibition of nitric oxide synthase (NOS). We hypothesized that the contribution of ROCK to reflex vasoconstriction (VC) is greater in aged skin. Cutaneous VC was elicited by 1) whole body cooling [mean skin temperature (Tsk) = 30.5°C] and 2) local norepinephrine (NE) infusion (1 x 10–6 M). Four microdialysis fibers were placed in the forearm skin of eight young (Y) and eight older (O) subjects for infusion of 1) Ringer solution (control), 2) 3 mM fasudil (ROCK inhibition), 3) 20...
Source: AJP: Heart and Circulatory Physiology - October 26, 2009 Category: Cardiology Authors: Lang, J. A., Jennings, J. D., Holowatz, L. A., Kenney, W. L. Tags: ARTICLES Source Type: journals
Role of tetrahydrobiopterin in resistance to myocardial ischemia in Brown Norway and Dahl S ratsEmail this article to a colleague.
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Previously we showed that Brown Norway (BN/Mcw) rats are more resistant to myocardial ischemia-reperfusion (I/R) injury than Dahl S (SS/Mcw) rats due to increased nitric oxide (·NO) generation secondary to increased heat shock protein 90 (HSP90) association with endothelial nitric oxide synthase (NOS3). Here we determined whether increased resistance to I/R injury in BN/Mcw hearts is also related to tetrahydrobiopterin (BH4) and GTP cyclohydrolase I (GCH-1), the rate-limiting enzyme for BH4 synthesis. We observed that BH4 supplementation via sepiapterin (SP) and inhibition of GCH-1 via 2,4-diamino-6-hydroxypyrimidin...
Source: AJP: Heart and Circulatory Physiology - October 26, 2009 Category: Cardiology Authors: An, J., Du, J., Wei, N., Xu, H., Pritchard, K. A., Shi, Y. Tags: ARTICLES Source Type: journals
Adenylyl cyclase type 5 protein expression during cardiac development and stressEmail this article to a colleague.
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Adenylyl cyclase (AC) types 5 and 6 (AC5 and AC6) are the two major AC isoforms expressed in the mammalian heart that mediate signals from β-adrenergic receptor stimulation. Because of the unavailability of isoform-specific antibodies, it is difficult to ascertain the expression levels of AC5 protein in the heart. Here we demonstrated the successful generation of an AC5 isoform-specific mouse monoclonal antibody and studied the expression of AC5 protein during cardiac development in different mammalian species. The specificity of the antibody was confirmed using heart and brain tissues from AC5 knockout mice and from ...
Source: AJP: Heart and Circulatory Physiology - October 26, 2009 Category: Cardiology Authors: Hu, C.-L., Chandra, R., Ge, H., Pain, J., Yan, L., Babu, G., Depre, C., Iwatsubo, K., Ishikawa, Y., Sadoshima, J., Vatner, S. F., Vatner, D. E. Tags: ARTICLES Source Type: journals
Activation of the PDK-1/Akt/eNOS pathway involved in aortic endothelial function differs between hyperinsulinemic and insulin-deficient diabetic ratsEmail this article to a colleague.
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In diabetic states, altered plasma insulin is likely to play key roles in 3-phosphoinositide-dependent protein kinase (PDK)/Akt pathway activation, in insulin resistance and in endothelial dysfunction. Since the molecular mechanism(s) remains unclear, we examined the relationship between the PDK/Akt/endothelial nitric oxide synthase (NOS) pathway and endothelial function in aortas from diabetic rats that were either insulin deficient or hyperinsulinemic. Untreated diabetic (diabetic) rats exhibited hyperglycemia and hypoinsulinemia, whereas high-insulin-treated diabetic (HI-diabetic) rats exhibited hyperinsulinemia. Aortas...
Source: AJP: Heart and Circulatory Physiology - October 26, 2009 Category: Cardiology Authors: Kobayashi, T., Taguchi, K., Nemoto, S., Nogami, T., Matsumoto, T., Kamata, K. Tags: ARTICLES Source Type: journals
Dissociation between reflex sympathetic and forearm vascular responses to lower body negative pressure in heart failure patients with coronary artery diseaseEmail this article to a colleague.
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Many heart failure (HF) patients exhibit paradoxical forearm vasodilation when central blood volume is reduced by lower body negative pressure (LBNP). We tested the hypothesis that this response results from reflex sympathetic withdrawal. We recorded simultaneously forearm blood flow, muscle sympathetic nerve activity (MSNA), and plasma norepinephrine (PNE) during four random applications of LBNP, –5, –10, –20, and –40 mmHg, in 12 men with HF (mean left ventricular ejection fraction = 24 ± 2%) and 10 healthy, normal, age-matched men (N). Compared with N, MSNA burst frequency (P = 0.001) and P...
Source: AJP: Heart and Circulatory Physiology - October 26, 2009 Category: Cardiology Authors: Notarius, C. F., Morris, B. L., Floras, J. S. Tags: ARTICLES Source Type: journals
Right ventricular pacing improves right heart function in experimental pulmonary arterial hypertension: a study in the isolated heartEmail this article to a colleague.
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Right heart failure in pulmonary arterial hypertension (PH) is associated with mechanical ventricular dyssynchrony, which leads to impaired right ventricular (RV) function and, by adverse diastolic interaction, to impaired left ventricular (LV) function as well. However, therapies aiming to restore synchrony by pacing are currently not available. In this proof-of-principle study, we determined the acute effects of RV pacing on ventricular dyssynchrony in PH. Chronic PH with right heart failure was induced in rats by injection of monocrotaline (80 mg/kg). To validate for PH-related ventricular dyssynchrony, rats (6 PH, 6 co...
Source: AJP: Heart and Circulatory Physiology - October 26, 2009 Category: Cardiology Authors: Handoko, M. L., Lamberts, R. R., Redout, E. M., de Man, F. S., Boer, C., Simonides, W. S., Paulus, W. J., Westerhof, N., Allaart, C. P., Vonk-Noordegraaf, A. Tags: ARTICLES Source Type: journals
Calpain inhibition preserves myocardial structure and function following myocardial infarctionEmail this article to a colleague.
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Cardiac pathology, such as myocardial infarction (MI), activates intracellular proteases that often trigger programmed cell death and contribute to maladaptive changes in myocardial structure and function. To test whether inhibition of calpain, a Ca2+-dependent cysteine protease, would prevent these changes, we used a mouse MI model. Calpeptin, an aldehydic inhibitor of calpain, was intravenously administered at 0.5 mg/kg body wt before MI induction and then at the same dose subcutaneously once per day. Both calpeptin-treated (n = 6) and untreated (n = 6) MI mice were used to study changes in myocardial structure and funct...
Source: AJP: Heart and Circulatory Physiology - October 26, 2009 Category: Cardiology Authors: Mani, S. K., Balasubramanian, S., Zavadzkas, J. A., Jeffords, L. B., Rivers, W. T., Zile, M. R., Mukherjee, R., Spinale, F. G., Kuppuswamy, D. Tags: ARTICLES Source Type: journals
Left ventricular function of isoproterenol-induced hypertrophied rat hearts perfused with blood: mechanical work and energeticsEmail this article to a colleague.
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We investigated left ventricular (LV) mechanical work and energetics in the cross-circulated (blood-perfused) isoproterenol [Iso 1.2 mg·kg–1·day–1 for 3 days (Iso3) or 7 days (Iso7)]-induced hypertrophied rat heart preparation under isovolumic contraction-relaxation. We evaluated pressure-time curves per beat, end-systolic pressure-volume and end-diastolic pressure-volume relations, and myocardial O2 consumption per beat (Vo2)-systolic pressure-volume area (PVA; a total mechanical energy per beat) linear relations at 240 beats/min, because Iso-induced hypertrophied hearts failed to completely rela...
Source: AJP: Heart and Circulatory Physiology - October 26, 2009 Category: Cardiology Authors: Nakajima-Takenaka, C., Zhang, G.-X., Obata, K., Tohne, K., Matsuyoshi, H., Nagai, Y., Nishiyama, A., Takaki, M. Tags: ARTICLES Source Type: journals
Cholesterol diet-induced hyperlipidemia impairs the cardioprotective effect of postconditioning: role of peroxynitriteEmail this article to a colleague.
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The aim of the present study was to investigate if hyperlipidemia interferes with the infarct size-limiting effect of postconditioning and to study the involvement of peroxynitrite in this phenomenon. Rats were fed a 2% cholesterol-enriched or normal diet for 12 wk. Infarct size by triphenyltetrazolium chloride staining was measured in hearts isolated from both groups and subjected to 30 min coronary occlusion followed by 120 min reperfusion with or without the postconditioning protocol induced by six cycles of 10 s coronary occlusion and 10 s reperfusion at the onset of the reperfusion. Postconditioning significantly decr...
Source: AJP: Heart and Circulatory Physiology - October 26, 2009 Category: Cardiology Authors: Kupai, K., Csonka, C., Fekete, V., Odendaal, L., van Rooyen, J., Marais, D. W., Csont, T., Ferdinandy, P. Tags: ARTICLES Source Type: journals
Microvascular oxygen delivery-to-utilization mismatch at the onset of heavy-intensity exercise in optimally treated patients with CHFEmail this article to a colleague.
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Impaired muscle blood flow at the onset of heavy-intensity exercise may transiently reduce microvascular O2 pressure and decrease the rate of O2 transfer from capillary to mitochondria in chronic heart failure (CHF). However, advances in the pharmacological treatment of CHF (e.g., angiotensin-converting enzyme inhibitors and third-generation β-blockers) may have improved microvascular O2 delivery to an extent that intramyocyte metabolic inertia might become the main locus of limitation of O2 uptake (Vo2) kinetics. We assessed the rate of change of pulmonary Vo2 (Vo2p), (estimated) fractional O2 extraction in the vastu...
Source: AJP: Heart and Circulatory Physiology - October 26, 2009 Category: Cardiology Authors: Sperandio, P. A., Borghi-Silva, A., Barroco, A., Nery, L. E., Almeida, D. R., Neder, J. A. Tags: ARTICLES Source Type: journals
O-GlcNAc signaling attenuates ER stress-induced cardiomyocyte deathEmail this article to a colleague.
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We previously demonstrated that the O-linked β-N-acetylglucosamine (O-GlcNAc) posttranslational modification confers cardioprotection at least partially through mitochondrial-dependent mechanisms, but it remained unclear if O-GlcNAc signaling interfered with other mechanisms of cell death. Because ischemia/hypoxia causes endoplasmic reticulum (ER) stress, we ascertained whether O-GlcNAc signaling could attenuate ER stress-induced cell death per se. Before induction of ER stress (with tunicamycin or brefeldin A), we adenovirally overexpressed O-GlcNAc transferase (AdOGT) or pharmacologically inhibited O-GlcNAcase [via ...
Source: AJP: Heart and Circulatory Physiology - October 26, 2009 Category: Cardiology Authors: Ngoh, G. A., Hamid, T., Prabhu, S. D., Jones, S. P. Tags: ARTICLES Source Type: journals
Regulation of VASP phosphorylation in cardiac myocytes: differential regulation by cyclic nucleotides and modulation of protein expression in diabetic and hypertrophic heartEmail this article to a colleague.
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Vasodilator-stimulated phosphoprotein (VASP) is a major substrate for cyclic nucleotide-dependent kinases that has been implicated in cardiac pathology, yet many aspects of VASP's molecular regulation in cardiomyocytes are incompletely understood. In these studies, we explored the role of VASP, both in signaling pathways in isolated murine myocytes, as well as in a model of cardiac hypertrophy in VASPnull mice. We found that the β-adrenergic agonist isoproterenol promotes the rapid and reversible phosphorylation of VASP at Ser157 and Ser239. Forskolin and the cAMP analog 8-(4-chlorophenylthio)-cAMP promote a similar p...
Source: AJP: Heart and Circulatory Physiology - October 26, 2009 Category: Cardiology Authors: Sartoretto, J. L., Jin, B. Y., Bauer, M., Gertler, F. B., Liao, R., Michel, T. Tags: ARTICLES Source Type: journals
VEGF-C regulates lymphangiogenesis and capillary stability by regulation of PDGF-BEmail this article to a colleague.
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Emerging evidence indicates that the tight communication between vascular endothelial cells and mural cells using platelet-derived growth factor (PDGF)-BB is essential for capillary stabilization during the angiogenic process. However, little is known about the related regulator that determines PDGF-BB expression. Using murine models of therapeutic neovascularization, we here show that a typical lymphangiogenic factor, vascular endothelial growth factor (VEGF)-C, is an essential regulator determining PDGF-BB expression for vascular stabilization via a paracrine mode of action. The blockade of VEGF type 3 receptor (VEGFR3) ...
Source: AJP: Heart and Circulatory Physiology - October 26, 2009 Category: Cardiology Authors: Onimaru, M., Yonemitsu, Y., Fujii, T., Tanii, M., Nakano, T., Nakagawa, K., Kohno, R.-i., Hasegawa, M., Nishikawa, S.-i., Sueishi, K. Tags: ARTICLES Source Type: journals
Replicative senescence of vascular smooth muscle cells enhances the calcification through initiating the osteoblastic transitionEmail this article to a colleague.
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Medial artery calcification, which does not accompany lipid or cholesterol deposit, preferentially occurs in elderly population, but its underlying mechanisms remain unclear. In the present study, we investigated the potential role of senescent vascular smooth muscle cells (VSMCs) in the formation of senescence-associated medial calcification. Replicative senescence was induced by the extended passages (until passages 11–13) in human primary VSMCs, and cells in early passage (passage 6) were used as control young cells. VSMC calcification was markedly enhanced in the senescent cells compared with that in the control ...
Source: AJP: Heart and Circulatory Physiology - October 26, 2009 Category: Cardiology Authors: Nakano-Kurimoto, R., Ikeda, K., Uraoka, M., Nakagawa, Y., Yutaka, K., Koide, M., Takahashi, T., Matoba, S., Yamada, H., Okigaki, M., Matsubara, H. Tags: ARTICLES Source Type: journals
Vasopressin is a major vasoconstrictor involved in hindlimb vascular responses to stimulation of adenosine A1 receptors in the nucleus of the solitary tractEmail this article to a colleague.
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Our previous study showed that stimulation of adenosine A1 receptors located in the nucleus of the solitary tract (NTS) exerts counteracting effects on the iliac vascular bed: activation of the adrenal medulla and β-adrenergic vasodilation versus vasoconstriction mediated by neural and unknown humoral factors. In the present study we investigated the relative contribution of three major potential humoral vasoconstrictors: vasopressin, angiotensin II, and norepinephrine in this response. In urethane-chloralose anesthetized rats we compared the integral changes in iliac vascular conductance evoked by microinjections int...
Source: AJP: Heart and Circulatory Physiology - October 26, 2009 Category: Cardiology Authors: McClure, J. M., Rossi, N. F., Chen, H., O'Leary, D. S., Scislo, T. J. Tags: ARTICLES Source Type: journals
Absence of adenosine-mediated aortic relaxation in A2A adenosine receptor knockout miceEmail this article to a colleague.
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In conclusion, A2AAR KO mice had significantly lower aortic relaxation and endothelial function, suggesting that the A2AAR plays an important role in vasorelaxation, probably through an endothelium-dependent mechanism. (Source: AJP: Heart and Circulatory Physiology)
Source: AJP: Heart and Circulatory Physiology - October 26, 2009 Category: Cardiology Authors: Ponnoth, D. S., Sanjani, M. S., Ledent, C., Roush, K., Krahn, T., Mustafa, S. J. Tags: ARTICLES Source Type: journals
Disruption of endothelial peroxisome proliferator-activated receptor-{gamma} reduces vascular nitric oxide productionEmail this article to a colleague.
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Vascular endothelial cells express the ligand-activated transcription factor, peroxisome proliferator-activated receptor- (PPAR), which participates in the regulation of metabolism, cell proliferation, and inflammation. PPAR ligands attenuate, whereas the loss of function mutations in PPAR stimulate, endothelial dysfunction, suggesting that PPAR may regulate vascular endothelial nitric oxide production. To explore the role of endothelial PPAR in the regulation of vascular nitric oxide production in vivo, mice expressing Cre recombinase driven by an endothelial-specific promoter were crossed with mice carrying a floxed PPAR...
Source: AJP: Heart and Circulatory Physiology - October 26, 2009 Category: Cardiology Authors: Kleinhenz, J. M., Kleinhenz, D. J., You, S., Ritzenthaler, J. D., Hansen, J. M., Archer, D. R., Sutliff, R. L., Hart, C. M. Tags: ARTICLES Source Type: journals
Protective actions of estrogen on angiotensin II-induced hypertension: role of central nitric oxideEmail this article to a colleague.
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The present study tested the hypotheses that 1) nitric oxide (NO) is involved in attenuated responses to ANG II in female mice, and 2) there is differential expression of neuronal NO synthase (nNOS) in the subfornical organ (SFO) and paraventricular nucleus (PVN) in response to systemic infusions of ANG II in males vs. females. Aortic blood pressure (BP) was measured in conscious mice with telemetry implants. NG-nitro-l-arginine methyl ester (l-NAME; 100 µg·kg·–1day–1), an inhibitor of NOS, was administrated into the lateral cerebral ventricle for 14 days before and during ANG II pump implan...
Source: AJP: Heart and Circulatory Physiology - October 26, 2009 Category: Cardiology Authors: Xue, B., Singh, M., Guo, F., Hay, M., Johnson, A. K. Tags: ARTICLES Source Type: journals
Impaired function of coronary BKCa channels in metabolic syndromeEmail this article to a colleague.
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The role of large-conductance Ca2+-activated K+ (BKCa) channels in regulation of coronary microvascular function is widely appreciated, but molecular and functional changes underlying the deleterious influence of metabolic syndrome (MetS) have not been determined. Male Ossabaw miniature swine consumed for 3–6 mo a normal diet (11% kcal from fat) or an excess-calorie atherogenic diet that induces MetS (45% kcal from fat, 2% cholesterol, 20% kcal from fructose). MetS significantly impaired coronary vasodilation to the BKCa opener NS-1619 in vivo (30–100 µg) and reduced the contribution of these channels to ...
Source: AJP: Heart and Circulatory Physiology - October 26, 2009 Category: Cardiology Authors: Borbouse, L., Dick, G. M., Asano, S., Bender, S. B., Dincer, U. D., Payne, G. A., Neeb, Z. P., Bratz, I. N., Sturek, M., Tune, J. D. Tags: ARTICLES Source Type: journals
Outflow tract cushions perform a critical valve-like function in the early embryonic heart requiring BMPRIA-mediated signaling in cardiac neural crestEmail this article to a colleague.
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This study provides definitive evidence that the outflow cushions perform a valve-like function critical for survival of the early mouse embryo. (Source: AJP: Heart and Circulatory Physiology)
Source: AJP: Heart and Circulatory Physiology - October 26, 2009 Category: Cardiology Authors: Nomura-Kitabayashi, A., Phoon, C. K. L., Kishigami, S., Rosenthal, J., Yamauchi, Y., Abe, K., Yamamura, K.-i., Samtani, R., Lo, C. W., Mishina, Y. Tags: ARTICLES Source Type: journals
Allogenic stem cell therapy improves right ventricular function by improving lung pathology in rats with pulmonary hypertensionEmail this article to a colleague.
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Pulmonary arterial hypertension (PAH) is a chronic lung disease that leads to right ventricular (RV) hypertrophy (RVH), remodeling, and failure. We tested treatment with bone marrow-derived mesenchymal stem cells (MSCs) obtained from donor rats with monocrotaline (MCT)-induced PAH to recipient rats with MCT-induced PAH on pulmonary artery pressure, lung pathology, and RV function. This model was chosen to mimic autologous MSC therapy. On day 1, PAH was induced by MCT (60 mg/kg) in 20 female Wistar rats. On day 14, rats were treated with 106 MSCs intravenously (MCT + MSC) or with saline (MCT60). MSCs were obtained from dono...
Source: AJP: Heart and Circulatory Physiology - October 26, 2009 Category: Cardiology Authors: Umar, S., de Visser, Y. P., Steendijk, P., Schutte, C. I., Laghmani, E. H., Wagenaar, G. T. M., Bax, W. H., Mantikou, E., Pijnappels, D. A., Atsma, D. E., Schalij, M. J., van der Wall, E. E., van der Laarse, A. Tags: TRANSLATIONAL PHYSIOLOGY Source Type: journals
Increased susceptibility of aged hearts to ventricular fibrillation during oxidative stressEmail this article to a colleague.
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Oxidative stress with hydrogen peroxide (H2O2) readily promotes early afterdepolarizations (EADs) and triggered activity (TA) in isolated rat and rabbit ventricular myocytes. Here we examined the effects of H2O2 on arrhythmias in intact Langendorff rat and rabbit hearts using dual-membrane voltage and intracellular calcium optical mapping and glass microelectrode recordings. Young adult rat (3–5 mo, N = 25) and rabbit (3–5 mo, N = 6) hearts exhibited no arrhythmias when perfused with H2O2 (0.1–2 mM) for up to 3 h. However, in 33 out of 35 (94%) aged (24–26 mo) rat hearts, 0.1 mM H2O2 caused EAD-medi...
Source: AJP: Heart and Circulatory Physiology - October 26, 2009 Category: Cardiology Authors: Morita, N., Sovari, A. A., Xie, Y., Fishbein, M. C., Mandel, W. J., Garfinkel, A., Lin, S.-F., Chen, P.-S., Xie, L.-H., Chen, F., Qu, Z., Weiss, J. N., Karagueuzian, H. S. Tags: TRANSLATIONAL PHYSIOLOGY Source Type: journals
A high-fat diet increases adiposity but maintains mitochondrial oxidative enzymes without affecting development of heart failure with pressure overloadEmail this article to a colleague.
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In conclusion, a high-fat diet did not worsen cardiac hypertrophy or left ventricular chamber enlargement despite increases in fat mass and insulin and leptin concentrations. Furthermore, a high-fat diet preserved MCAD and citrate synthase activities during pressure overload, suggesting that it may help maintain mitochondrial oxidative capacity in failing myocardium. (Source: AJP: Heart and Circulatory Physiology)
Source: AJP: Heart and Circulatory Physiology - October 26, 2009 Category: Cardiology Authors: Chess, D. J., Khairallah, R. J., O'Shea, K. M., Xu, W., Stanley, W. C. Tags: TRANSLATIONAL PHYSIOLOGY Source Type: journals
A new piece in the hypertension puzzle: central blood pressure regulation by sex steroidsEmail this article to a colleague.
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(Source: AJP: Heart and Circulatory Physiology)
Source: AJP: Heart and Circulatory Physiology - October 26, 2009 Category: Cardiology Authors: Yanes, L. L., Reckelhoff, J. F. Tags: EDITORIAL FOCUS Source Type: journals
BK channels in cardiovascular disease: a complex story of channel dysregulationEmail this article to a colleague.
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(Source: AJP: Heart and Circulatory Physiology)
Source: AJP: Heart and Circulatory Physiology - October 26, 2009 Category: Cardiology Authors: Rusch, N. J. Tags: EDITORIAL FOCUS Source Type: journals
Pathways to embryonic heart failureEmail this article to a colleague.
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(Source: AJP: Heart and Circulatory Physiology)
Source: AJP: Heart and Circulatory Physiology - October 26, 2009 Category: Cardiology Authors: Sedmera, D. Tags: EDITORIAL FOCUS Source Type: journals
Calcineurin and cardiac function: is more or less better for the heart?Email this article to a colleague.
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(Source: AJP: Heart and Circulatory Physiology)
Source: AJP: Heart and Circulatory Physiology - October 26, 2009 Category: Cardiology Authors: Wolska, B. M. Tags: EDITORIAL FOCUS Source Type: journals
Angiotensin II, mechanotransduction, and pulsatile arterial hemodynamics in hypertensionEmail this article to a colleague.
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The aortic blood pressure curve involves two components: a steady component, the mean arterial pressure (MAP), which is dependent on cardiac output and vascular resistance, and a pulsatile component pulse pressure (PP), which is dependent on arterial stiffness and pulse wave reflections. The transduction mechanisms of MAP and PP differ markedly, involving focal adhesion kinase for MAP and oxygen free radicals for PP. Angiotensin II (ANG II) and its blockade are associated with changed vascular resistance and MAP; however, their effects on PP (peripheral and mostly central PP) have been inadequately investigated. In hyperte...
Source: AJP: Heart and Circulatory Physiology - October 26, 2009 Category: Cardiology Authors: Lacolley, P., Safar, M. E., Regnault, V., Frohlich, E. D. Tags: REVIEW Source Type: journals
Regulation of central angiotensin type 1 receptors and sympathetic outflow in heart failureEmail this article to a colleague.
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Angiotensin type 1 receptors (AT1Rs) play a critical role in a variety of physiological functions and pathophysiological states. They have been strongly implicated in the modulation of sympathetic outflow in the brain. An understanding of the mechanisms by which AT1Rs are regulated in a variety of disease states that are characterized by sympathoexcitation is pivotal in development of new strategies for the treatment of these disorders. This review concentrates on several aspects of AT1R regulation in the setting of chronic heart failure (CHF). There is now good evidence that AT1R expression in neurons is mediated by activ...
Source: AJP: Heart and Circulatory Physiology - October 26, 2009 Category: Cardiology Authors: Zucker, I. H., Schultz, H. D., Patel, K. P., Wang, W., Gao, L. Tags: REVIEW Source Type: journals
