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This page shows you the most recent publications within this specialty of the MedWorm directory. This is page number 21.

Tetrahydrobiopterin increases NO-dependent vasodilation in hypercholesterolemic human skin through eNOS-coupling mechanisms
Localized exogenous R-tetrahydrobiopterin (R-BH4) corrects the deficit in local heat-induced vasodilation (VD) in hypercholesterolemic (HC) human skin through one of two plausible mechanisms: by serving as an essential cofactor to stabilizing endothelial nitric oxide (NO) synthase (eNOS) or through generalized antioxidant effects. We used the stereoisomer S-BH4, which has the same antioxidant properties but does not function as an essential NOS cofactor, to elucidate the mechanism by which R-BH4 restores cutaneous VD in HC humans. Intradermal microdialysis fibers were placed in 20 normocholesterolemic (NC), 13 midrange cho...
Source: AJP: Regulatory, Integrative and Comparative Physiology - January 15, 2013 Category: Physiology Authors: Alexander, L. M., Kutz, J. L., Kenney, W. L. Tags: Cardiovascular and Renal Integration Source Type: research

SK channel-selective opening by SKA-31 induces hyperpolarization and decreases contractility in human urinary bladder smooth muscle
Overactive bladder (OAB) is often associated with increased involuntary detrusor smooth muscle (DSM) contractions during the bladder-filling phase. To develop novel therapies for OAB, it is critical to better understand the mechanisms that control DSM excitability and contractility. Recent studies showed that small-conductance Ca2+-activated K+ (SK) channels, SK3 channels, in particular, regulate human DSM function. However, the concept that SK channel-selective pharmacological activation can decrease the excitability and contractility directly in human DSM needs further exploration. Here, we studied the effect of the nove...
Source: AJP: Regulatory, Integrative and Comparative Physiology - January 15, 2013 Category: Physiology Authors: Soder, R. P., Parajuli, S. P., Hristov, K. L., Rovner, E. S., Petkov, G. V. Tags: Cardiovascular and Renal Integration Source Type: research

Initial orthostatic hypotension and cerebral blood flow regulation: effect of {alpha}1-adrenoreceptor activity
We examined the hypothesis that α1-adrenergic blockade would lead to an inability to correct initial orthostatic hypotension (IOH) and cerebral hypoperfusion, leading to symptoms of presyncope. Twelve normotensive humans (aged 25 ± 1 yr; means ± SE) attempted to complete a 3-min upright stand, 90 min after the administration of either α1-blockade (prazosin, 1 mg/20 kg body wt) or placebo. Continuous beat-to-beat measurements of middle cerebral artery velocity (MCAv; Doppler), blood pressure (finometer), heart rate, and end-tidal Pco2 were obtained. Compared with placebo, the α1-blockade redu...
Source: AJP: Regulatory, Integrative and Comparative Physiology - January 15, 2013 Category: Physiology Authors: Lewis, N. C. S., Ainslie, P. N., Atkinson, G., Jones, H., Grant, E. J. M., Lucas, S. J. E. Tags: Cardiovascular and Renal Integration Source Type: research

Effect of chronic perinatal hypoxia on the role of rho-kinase in pulmonary artery contraction in newborn lambs
Exposure to chronic hypoxia during gestation predisposes infants to neonatal pulmonary hypertension, but the underlying mechanisms remain unclear. Here, we test the hypothesis that moderate continuous hypoxia during gestation causes changes in the rho-kinase pathway that persist in the newborn period, altering vessel tone and responsiveness. Lambs kept at 3,801 m above sea level during gestation and the first 2 wk of life were compared with those with gestation at low altitude. In vitro studies of isolated pulmonary arterial rings found a more forceful contraction in response to KCl and 5-HT in high-altitude compared with ...
Source: AJP: Regulatory, Integrative and Comparative Physiology - January 15, 2013 Category: Physiology Authors: Blood, A. B., Terry, M. H., Merritt, T. A., Papamatheakis, D. G., Blood, Q., Ross, J. M., Power, G. G., Longo, L. D., Wilson, S. M. Tags: Hormones, Reproduction and Development Source Type: research

Control of soluble fms-like tyrosine-1 (sFlt-1) production response to placental ischemia/hypoxia: role of tumor necrosis factor-{alpha}
Although abnormal soluble fms-like tyrosine kinase-1 (sFlt-1) production is thought to be an important factor in the pathogenesis of preeclampsia (PE), the mechanisms that regulate the production of sFlt-1 during PE are unclear. While our laboratory has shown tumor necrosis factor-α (TNF-α) and sFlt-1 to be elevated in pregnant rats in response to placental ischemia, the importance of TNF-α in the regulation of sFlt-1 production is unknown. Therefore, the purpose of this study was to determine the role of TNF-α in mediating the increase in sFlt-1 in response to placental ischemia or hypoxia. Reducti...
Source: AJP: Regulatory, Integrative and Comparative Physiology - January 15, 2013 Category: Physiology Authors: Murphy, S. R., LaMarca, B. B. D., Parrish, M., Cockrell, K., Granger, J. P. Tags: Cardiovascular and Renal Integration Source Type: research

Early life stress induces renal dysfunction in adult male rats but not female rats
We reported that MatSep exacerbates ANG II-induced hypertension in adult male rats. The aims of this study were to determine whether exposure to MatSep in female rats sensitizes blood pressure to ANG II infusion similar to male MatSep rats and to elucidate renal mechanisms involved in the response in MatSep rats. Wistar Kyoto (WKY) pups were exposed to MatSep 3 h/day from days 2 to 14, while control rats remained with their mothers. ANG II-induced mean arterial pressure (MAP; telemetry) was enhanced in female MatSep rats compared with control female rats but delayed compared with male MatSep rats. Creatinine clearance (Ccr...
Source: AJP: Regulatory, Integrative and Comparative Physiology - January 15, 2013 Category: Physiology Authors: Loria, A. S., Yamamoto, T., Pollock, D. M., Pollock, J. S. Tags: Hormones, Reproduction and Development Source Type: research

Phycocyanin and phycocyanobilin from Spirulina platensis protect against diabetic nephropathy by inhibiting oxidative stress
In conclusion, oral administration of phycocyanin and phycocyanobilin may offer a novel and feasible therapeutic approach for preventing diabetic nephropathy.
Source: AJP: Regulatory, Integrative and Comparative Physiology - January 15, 2013 Category: Physiology Authors: Zheng, J., Inoguchi, T., Sasaki, S., Maeda, Y., McCarty, M. F., Fujii, M., Ikeda, N., Kobayashi, K., Sonoda, N., Takayanagi, R. Tags: Cardiovascular and Renal Integration Source Type: research

Differential expression of the pro-natriuretic peptide convertases corin and furin in experimental heart failure and atrial fibrosis
In heart failure (HF), the cardiac hormone natriuretic peptides (NPs) atrial (ANP), B-type (BNP), and C-type (CNP) play a key role to protect cardiac remodeling. The proprotein convertases corin and furin process their respective pro-NPs into active NPs. Here we define in a canine model of HF furin and corin gene and protein expression in normal and failing left atrium (LA) or ventricle (LV) testing the hypothesis that the NP proproteins convertases production is altered in experimental HF. Experimental canine HF was produced by rapid right ventricular pacing for 10 days. NPs, furin, and corin mRNA expression were determin...
Source: AJP: Regulatory, Integrative and Comparative Physiology - January 15, 2013 Category: Physiology Authors: Ichiki, T., Boerrigter, G., Huntley, B. K., Sangaralingham, S. J., McKie, P. M., Harty, G. J., Harders, G. E., Burnett, J. C. Tags: Hormones, Reproduction and Development Source Type: research

Nighttime snacking reduces whole body fat oxidation and increases LDL cholesterol in healthy young women
We examined the effects of nighttime snacking for 13 days on energy metabolism. Eleven healthy women (means ± SD; age: 23 ± 1 yr; body mass index: 20.6 ± 2.6 kg/m2) participated in this randomized crossover trial for a 13-day intervention period. Subjects consumed a specified snack (192.4 ± 18.3 kcal) either during the daytime (10:00) or the night time (23:00) for 13 days. On day 14, energy metabolism was measured in a respiratory chamber without snack consumption. An oral glucose tolerance test was performed on day 15. Relative to daytime snacking, nighttime snacking significantly decreased fat...
Source: AJP: Regulatory, Integrative and Comparative Physiology - January 15, 2013 Category: Physiology Authors: Hibi, M., Masumoto, A., Naito, Y., Kiuchi, K., Yoshimoto, Y., Matsumoto, M., Katashima, M., Oka, J., Ikemoto, S. Tags: Obesity, Diabetes and Energy Homeostasis Source Type: research

Impact of diabetes mellitus on bladder uroepithelial cells
Diabetic bladder dysfunction (DBD), a prevalent complication of diabetes mellitus (DM), is characterized by a broad spectrum of symptoms including urinary urgency, frequency, and incontinence. As DBD is commonly diagnosed late, it is important to understand the chronic impact of DM on bladder tissues. While changes in bladder smooth muscle and innervation have been reported in diabetic patients, the impact of DM on the specialized epithelial lining of the urinary bladder, the urothelium (UT), is largely unknown. Quantitative polymerase chain reaction analysis and electron microscopy were used to evaluate UT gene expression...
Source: AJP: Regulatory, Integrative and Comparative Physiology - January 15, 2013 Category: Physiology Authors: Hanna-Mitchell, A. T., Ruiz, G. W., Daneshgari, F., Liu, G., Apodaca, G., Birder, L. A. Tags: Obesity, Diabetes and Energy Homeostasis Source Type: research

Effects of short-term dietary nitrate supplementation on blood pressure, O2 uptake kinetics, and muscle and cognitive function in older adults
Dietary nitrate (NO3–) supplementation has been shown to reduce resting blood pressure and alter the physiological response to exercise in young adults. We investigated whether these effects might also be evident in older adults. In a double-blind, randomized, crossover study, 12 healthy, older (60–70 yr) adults supplemented their diet for 3 days with either nitrate-rich concentrated beetroot juice (BR; 2 x 70 ml/day, ~9.6 mmol/day NO3–) or a nitrate-depleted beetroot juice placebo (PL; 2 x 70 ml/day, ~0.01 mmol/day NO3–). Before and after the intervention periods, resting blood pressure and plasma ...
Source: AJP: Regulatory, Integrative and Comparative Physiology - January 15, 2013 Category: Physiology Authors: Kelly, J., Fulford, J., Vanhatalo, A., Blackwell, J. R., French, O., Bailey, S. J., Gilchrist, M., Winyard, P. G., Jones, A. M. Tags: Respiration Source Type: research

Corpus luteal contribution to maternal pregnancy physiology and outcomes in assisted reproductive technologies
Investigations in the rat model of pregnancy indicate an important role for the corpus luteal (CL) hormone relaxin in the maternal circulatory and osmoregulatory changes in pregnancy, which are epitomized by profound vasodilation and modest hypoosmolality, respectively. In a pilot study of infertile women who became pregnant through donor eggs, in vitro fertilization, and embryo transfer, the gestational rise in glomerular filtration and fall in plasma osmolality were markedly subdued. Because these women were infertile, they lacked a CL and circulating relaxin (and possibly other vasoactive CL hormones). Based on these fi...
Source: AJP: Regulatory, Integrative and Comparative Physiology - January 15, 2013 Category: Physiology Authors: Conrad, K. P., Baker, V. L. Tags: Perspectives Source Type: research

Annexin A1, a regulator of BBB integrity [Physiology]
The blood–brain barrier (BBB), a critical guardian of communication between the periphery and the brain, is frequently compromised in neurological diseases such as multiple sclerosis (MS), resulting in the inappropriate passage of molecules and leukocytes into the brain. Here we show that the glucocorticoid anti-inflammatory messenger annexin A1 (ANXA1) is...
Source: Proceedings of the National Academy of Sciences - January 15, 2013 Category: Science Authors: Cristante, E., McArthur, S., Mauro, C., Maggioli, E., Romero, I. A., Wylezinska-Arridge, M., Couraud, P. O., Lopez-Tremoleda, J., Christian, H. C., Weksler, B. B., Malaspina, A., Solito, E. Tags: Feature Articles Source Type: research

Nogo-A in cerebellar development and physiology [Neuroscience]
Neuronal signal integration as well as synaptic transmission and plasticity highly depend on the morphology of dendrites and their spines. Nogo-A is a membrane protein enriched in the adult central nervous system (CNS) myelin, where it restricts the capacity of axons to grow and regenerate after injury. Nogo-A is also...
Source: Proceedings of the National Academy of Sciences - January 15, 2013 Category: Science Authors: Petrinovic, M. M., Hourez, R., Aloy, E. M., Dewarrat, G., Gall, D., Weinmann, O., Gaudias, J., Bachmann, L. C., Schiffmann, S. N., Vogt, K. E., Schwab, M. E. Tags: Biological Sciences Source Type: research

Accelerated structural decrements in the aging female rhesus macaque lung compared with males
Aging is associated with morphometric changes in the lung that lead to decreased lung function. The nonhuman primate lung has been shown to have similar architectural, morphological, and developmental patterns to that of humans. We hypothesized that the lungs of rhesus monkeys age in a pattern similar to human lungs. Thirty-four rhesus monkeys from the California National Primate Research Center were euthanized, necropsied, and the whole lungs sampled. Stereological analysis was performed to assess the morphological changes associated with age. The number of alveoli declined significantly from age 9 to 33 yr with a greater...
Source: AJP: Lung Cellular and Molecular Physiology - January 15, 2013 Category: Respiratory Medicine Authors: Herring, M. J., Avdalovic, M. V., Quesenberry, C. L., Putney, L. F., Tyler, N. K., Ventimiglia, F. F., St. George, J. A., Hyde, D. M. Tags: ARTICLES Source Type: research

IL-13 receptor {alpha}2-arginase 2 pathway mediates IL-13-induced pulmonary hypertension
This study's goal was to investigate the role and mechanism of IL-13 in the pathogenesis of PH. Lung-specific IL-13-overexpressing transgenic (Tg) mice were examined for hemodynamic changes and pulmonary vascular remodeling. IL-13 Tg mice spontaneously developed PH phenotype by the age of 2 mo with increased expression and activity of arginase 2 (Arg2). The role of Arg2 in the development of IL-13-stimulated PH was further investigated using Arg2 and IL-13 receptor α2 (Rα2) null mutant mice and the small-interfering RNA (siRNA)-silencing approach in vivo and in vitro, respectively. IL-13-stimulated medial thick...
Source: AJP: Lung Cellular and Molecular Physiology - January 15, 2013 Category: Respiratory Medicine Authors: Cho, W.-K., Lee, C.-M., Kang, M.-J., Huang, Y., Giordano, F. J., Lee, P. J., Trow, T. K., Homer, R. J., Sessa, W. C., Elias, J. A., Lee, C. G. Tags: ARTICLES Source Type: research

Wnt5a inhibits hypoxia-induced pulmonary arterial smooth muscle cell proliferation by downregulation of {beta}-catenin
This study evaluated the effect of Wnt5a on hypoxia-induced proliferation of human PASMCs and its possible mechanism. The results show that hypoxia (3% O2, 48 h) induced proliferation of human PASMCs, accompanied with a significant decrease in Wnt5a gene expression, increase in β-catenin and Cyclin D1 expression, as well as β-catenin nuclear translocation. Treatment with recombinant mouse Wnt5a significantly inhibited hypoxia-induced proliferation of human PASMCs, upregulation of Cyclin D1 and β-catenin expression, as well as the nuclear translocation of β-catenin. These effects were inhibited by Wnt5a ...
Source: AJP: Lung Cellular and Molecular Physiology - January 15, 2013 Category: Respiratory Medicine Authors: Yu, X.-M., Wang, L., Li, J.-F., Liu, J., Li, J., Wang, W., Wang, J., Wang, C. Tags: ARTICLES Source Type: research

Differential susceptibility of inbred mouse strains to chlorine-induced airway fibrosis
Chlorine is a reactive gas that is considered a chemical threat agent. Humans who develop acute lung injury from chlorine inhalation typically recover normal lung function; however, a subset can experience chronic airway disease. To examine pathological changes following chlorine-induced lung injury, mice were exposed to a single high dose of chlorine, and repair of the lung was analyzed at multiple times after exposure. In FVB/NJ mice, chlorine inhalation caused pronounced fibrosis of larger airways that developed by day 7 after exposure and was associated with airway hyperreactivity. In contrast, A/J mice had little or n...
Source: AJP: Lung Cellular and Molecular Physiology - January 15, 2013 Category: Respiratory Medicine Authors: Mo, Y., Chen, J., Schlueter, C. F., Hoyle, G. W. Tags: ARTICLES Source Type: research

Automated measurement of blood flow velocity and direction and hemoglobin oxygen saturation in the rat lung using intravital microscopy
Intravital microscopy of the pulmonary microcirculation in research animals is of great scientific interest for its utility in identifying regional changes in pulmonary microcirculatory blood flow. Although feasibility studies have been reported, the pulmonary window can be further refined into a practical tool for pharmaceutical research and drug development. We have established a method to visualize and quantify dynamic changes in three key features of lung function: microvascular red blood cell velocity, flow direction, and hemoglobin saturation. These physiological parameters were measured in an acute closed-chest pulm...
Source: AJP: Lung Cellular and Molecular Physiology - January 15, 2013 Category: Respiratory Medicine Authors: Hanna, G., Fontanella, A., Palmer, G., Shan, S., Radiloff, D. R., Zhao, Y., Irwin, D., Hamilton, K., Boico, A., Piantadosi, C. A., Blueschke, G., Dewhirst, M., McMahon, T., Schroeder, T. Tags: INNOVATIVE METHODOLOGY Source Type: research

TGF-{beta}-Smad3 signaling in emphysema and pulmonary fibrosis: an epigenetic aberration of normal development?
It is well accepted that TGF-β signaling has critical functional roles in lung development, injury, and repair. We showed previously that null mutation of Smad3, a critical node in the TGF-β pathway, protects mice against fibrosis induced by bleomycin. However, more recently we noticed that abnormal alveolarization also occurs in Smad3-deficient mice and that this is followed by progressive emphysema-like alveolar wall destruction mediated by MMP9. We now know that Smad3 cooperates with c-Jun to synergistically regulate a protein deacetylase SIRT1, by binding to an AP-1 site in the SIRT1 promoter. Consistently, S...
Source: AJP: Lung Cellular and Molecular Physiology - January 15, 2013 Category: Respiratory Medicine Authors: Warburton, D., Shi, W., Xu, B. Tags: REVIEW Source Type: research

Acute Kidney Injury Following Coronary Artery Bypass Surgery and Long-term Risk of Heart Failure [Original Articles]
Conclusions— AKI is associated with increased long-term risk of HF after CABG. Patients with AKI after CABG should be followed closely to detect early changes in cardiac function.
Source: Circulation: Heart Failure - January 15, 2013 Category: Cardiology Authors: Olsson, D., Sartipy, U., Braunschweig, F., Holzmann, M. J. Tags: Cardio-renal physiology/pathophysiology, Congestive, CV surgery: coronary artery disease, Chronic ischemic heart disease, Epidemiology Original Articles Source Type: research

Hepatic overexpression of Abcb11 in mice promotes the conservation of bile acids within the enterohepatic circulation
The bile salt export pump, encoded by ABCB11, is the predominant canalicular transport protein for biliary bile acid secretion. The level of ABCB11 expression in humans is widely variable yet the impact of this variability on human disease is not well defined. We aim to determine the effect of hepatic Abcb11 overexpression on the enterohepatic circulation (EHC) in mice. We used a stable isotope dilution technique in transgenic mice overexpressing hepatic Abcb11 (TTR-Abcb11) to determine the pool size, fractional turnover rate (FTR), and synthesis rate of the primary bile acid, cholic acid (CA). The gallbladder was cannulat...
Source: AJP: Gastrointestinal and Liver Physiology - January 15, 2013 Category: Gastroenterology Authors: Henkel, A. S., Gooijert, K. E. R., Havinga, R., Boverhof, R., Green, R. M., Verkade, H. J. Tags: LIVER AND BILIARY TRACT Source Type: research

Psychoactive bacteria Lactobacillus rhamnosus (JB-1) elicits rapid frequency facilitation in vagal afferents
Mounting evidence supports the influence of the gut microbiome on the local enteric nervous system and its effects on brain chemistry and relevant behavior. Vagal afferents are involved in some of these effects. We previously showed that ingestion of the probiotic bacterium Lactobacillus rhamnosus (JB-1) caused extensive neurochemical changes in the brain and behavior that were abrogated by prior vagotomy. Because information can be transmitted to the brain via primary afferents encoded as neuronal spike trains, our goal was to record those induced by JB-1 in vagal afferents in the mesenteric nerve bundle and thus determin...
Source: AJP: Gastrointestinal and Liver Physiology - January 15, 2013 Category: Gastroenterology Authors: Perez-Burgos, A., Wang, B., Mao, Y.-K., Mistry, B., Neufeld, K.-A. M., Bienenstock, J., Kunze, W. Tags: NEUROREGULATION AND MOTILITY Source Type: research

D-Glucose modulates intestinal Niemann-Pick C1-like 1 (NPC1L1) gene expression via transcriptional regulation
In conclusion, glucose appears to directly modulate NPC1L1 expression via transcriptional mechanisms and the involvement of phosphatase-dependent pathways.
Source: AJP: Gastrointestinal and Liver Physiology - January 15, 2013 Category: Gastroenterology Authors: Malhotra, P., Boddy, C. S., Soni, V., Saksena, S., Dudeja, P. K., Gill, R. K., Alrefai, W. A. Tags: MUCOSAL BIOLOGY Source Type: research

The guggulsterone derivative GG-52 inhibits NF-{kappa}B signaling in gastric epithelial cells and ameliorates ethanol-induced gastric mucosal lesions in mice
Gastric mucosal inflammation can develop after challenge with noxious stimuli such as alcohol. Specially, alcohol stimulates the release of inflammatory cytokines but does not increase gastric acid secretion, leading to gastric mucosal damage. The plant sterol guggulsterone and its novel derivative GG-52 have been reported to inhibit nuclear factor-B (NF-B) signaling in intestinal epithelial cells and experimental colitis. In the present study, we investigated the anti-inflammatory effects of GG-52 on gastric epithelial cells and on ethanol-induced gastric mucosal inflammation in mice. GG-52 inhibited the expression of int...
Source: AJP: Gastrointestinal and Liver Physiology - January 15, 2013 Category: Gastroenterology Authors: Kim, J. M., Kim, S. H., Ko, S. H., Jung, J., Chun, J., Kim, N., Jung, H. C., Kim, J. S. Tags: INFLAMMATION/IMMUNITY/MEDIATORS Source Type: research

Activation of cannabinoid receptor 2 reduces inflammation in acute experimental pancreatitis via intra-acinar activation of p38 and MK2-dependent mechanisms
The endocannabinoid system has been shown to mediate beneficial effects on gastrointestinal inflammation via cannabinoid receptors 1 (CB1) and 2 (CB2). These receptors have also been reported to activate the MAP kinases p38 and c-Jun NH2-terminal kinase (JNK), which are involved in early acinar events leading to acute pancreatitis and induction of proinflammatory cytokines. Our aim was to examine the role of cannabinoid receptor activation in an experimental model of acute pancreatitis and the potential involvement of MAP kinases. Cerulein pancreatitis was induced in wild-type, CB1–/–, and MK2–/– mi...
Source: AJP: Gastrointestinal and Liver Physiology - January 15, 2013 Category: Gastroenterology Authors: Michler, T., Storr, M., Kramer, J., Ochs, S., Malo, A., Reu, S., Goke, B., Schafer, C. Tags: PANCREAS Source Type: research

Smad7 inhibits autocrine expression of TGF-{beta}2 in intestinal epithelial cells in baboon necrotizing enterocolitis
Preterm infants may be at risk of necrotizing enterocolitis (NEC) due to deficiency of transforming growth factor-β 2 (TGF-β2) in the developing intestine. We hypothesized that low epithelial TGF-β2 expression in preterm intestine and during NEC results from diminished autocrine induction of TGF-β2 in these cells. Premature baboons delivered at 67% gestation were treated per current norms for human preterm infants. NEC was diagnosed by clinical and radiological findings. Inflammatory cytokines, TGF-β2, Smad7, Ski, and strawberry notch N (SnoN)/Ski-like oncoprotein (SKIL) was measured using quantita...
Source: AJP: Gastrointestinal and Liver Physiology - January 15, 2013 Category: Gastroenterology Authors: Namachivayam, K., Blanco, C. L., MohanKumar, K., Jagadeeswaran, R., Vasquez, M., McGill-Vargas, L., Garzon, S. A., Jain, S. K., Gill, R. K., Freitag, N. E., Weitkamp, J.-H., Seidner, S. R., Maheshwari, A. Tags: INFLAMMATION/IMMUNITY/MEDIATORS Source Type: research

Independent trafficking of the KCNQ1 K+ channel and H+-K+-ATPase in gastric parietal cells from mice
Gastric acid secretion by the H+-K+-ATPase at the apical surface of activated parietal cells requires luminal K+ provided by the KCNQ1/KCNE2 K+ channel. However, little is known about the trafficking and relative spatial distribution of KCNQ1 and H+-K+-ATPase in resting and activated parietal cells and the capacity of KCNQ1 to control acid secretion. Here we show that inhibition of KCNQ1 activity quickly curtails gastric acid secretion in vivo, even when the H+-K+-ATPase is permanently anchored in the apical membrane, demonstrating a key role of the K+ channel in controlling acid secretion. Three-dimensional imaging analys...
Source: AJP: Gastrointestinal and Liver Physiology - January 15, 2013 Category: Gastroenterology Authors: Nguyen, N., Kozer-Gorevich, N., Gliddon, B. L., Smolka, A. J., Clayton, A. H., Gleeson, P. A., van Driel, I. R. Tags: MUCOSAL BIOLOGY Source Type: research

Capsaicin induces NKCC1 internalization and inhibits chloride secretion in colonic epithelial cells independently of TRPV1
Colonic chloride secretion is regulated via the neurohormonal and immune systems. Exogenous chemicals (e.g., butyrate, propionate) can affect chloride secretion. Capsaicin, the pungent ingredient of the chili peppers, exerts various effects on gastrointestinal function. Capsaicin is known to activate the transient receptor potential vanilloid type 1 (TRPV1), expressed in the mesenteric nervous system. Recent studies have also demonstrated its presence in epithelial cells but its role remains uncertain. Because capsaicin has been reported to inhibit colonic chloride secretion, we tested whether this effect of capsaicin coul...
Source: AJP: Gastrointestinal and Liver Physiology - January 15, 2013 Category: Gastroenterology Authors: Bouyer, P. G., Tang, X., Weber, C. R., Shen, L., Turner, J. R., Matthews, J. B. Tags: MUCOSAL BIOLOGY Source Type: research

Probiotics prevent necrotizing enterocolitis by modulating enterocyte genes that regulate innate immune-mediated inflammation
Necrotizing enterocolitis (NEC), an extensive intestinal inflammatory disease of premature infants, is caused, in part, by an excessive inflammatory response to initial bacterial colonization due to the immature expression of innate immune response genes. In a randomized placebo-controlled clinical trial, supplementation of very low birth weight infants with probiotics significantly reduced the incidence of NEC. The primary goal of this study was to determine whether secreted products of these two clinically effective probiotic strains, Bifidobacterium infantis and Lactobacillus acidophilus, prevented NEC by accelerating t...
Source: AJP: Gastrointestinal and Liver Physiology - January 15, 2013 Category: Gastroenterology Authors: Ganguli, K., Meng, D., Rautava, S., Lu, L., Walker, W. A., Nanthakumar, N. Tags: INFLAMMATION/IMMUNITY/MEDIATORS Source Type: research

Heterogeneous nuclear ribonucleoprotein A2/B1 is a tissue-specific aldosterone target gene with prominent induction in the rat distal colon
In this study, we examined whether hnRNP A2/B1 is an aldosterone-target gene in vivo. Our data show that physiological levels of aldosterone markedly induce hnRNP A2/B1 expression in an early and sustained manner in the late distal colon epithelium but not in other aldosterone-target tissues. The effect depends on MR but not on glucocorticoid receptor activity. We also demonstrate that the genomic region upstream of hnRNP A2/B1 contains aldosterone-responsive elements involved in the control of gene expression. We hypothesize that hnRNP A2/B1 is involved in the tissue-specific regulation of ENaC biosynthesis and may coordi...
Source: AJP: Gastrointestinal and Liver Physiology - January 15, 2013 Category: Gastroenterology Authors: Hernandez-Diaz, I., Giraldez, T., Morales, S., Hernandez, G., Salido, E., Canessa, C. M., Alvarez de la Rosa, D. Tags: HORMONES AND SIGNALING Source Type: research

Gastrokines: stomach-specific proteins with putative homeostatic and tumor suppressor roles
During the past decade, a new family of stomach-specific proteins has been recognized. Known as "gastrokines" (GKNs), these secreted proteins are products of gastric mucus-producing cell lineages. GKNs are highly conserved in physical structure, and emerging data point to convergent functions in the modulation of gastric mucosal homeostasis and inflammation. While GKNs are highly prevalent in the normal stomach, frequent loss of GKN expression in gastric cancers, coupled with established antiproliferative activity, suggests putative tumor suppressor roles. Conversely, ectopic expression of GKNs in reparative lesions of Cro...
Source: AJP: Gastrointestinal and Liver Physiology - January 15, 2013 Category: Gastroenterology Authors: Menheniott, T. R., Kurklu, B., Giraud, A. S. Tags: REVIEW Source Type: research

A novel hemoglobin-binding peptide reduces cell-free hemoglobin in murine hemolytic anemia
Hemolysis can saturate the hemoglobin (Hb)/heme scavenging system, resulting in increased circulating cell-free Hb (CF-Hb) in hereditary and acquired hemolytic disease. While recent studies have suggested a central role for intravascular hemolysis and CF-Hb in the development of vascular dysfunction, this concept has stimulated considerable debate. This highlights the importance of determining the contribution of CF-Hb to vascular complications associated with hemolysis. Therefore, a novel Hb-binding peptide was synthesized and linked to a small fragment of apolipoprotein E (amino acids 141–150) to facilitate endocyt...
Source: AJP: Heart and Circulatory Physiology - January 15, 2013 Category: Cardiology Authors: Hanson, M. S., Xu, H., Flewelen, T. C., Holzhauer, S. L., Retherford, D., Jones, D. W., Frei, A. C., Pritchard, K. A., Hillery, C. A., Hogg, N., Wandersee, N. J. Tags: INTEGRATIVE CARDIOVASCULAR PHYSIOLOGY AND PATHOPHYSIOLOGY Source Type: research

Hibernating myocardium results in partial sympathetic denervation and nerve sprouting
In conclusion, sympathetic nerve dysfunction in hibernating myocardium is most consistent with partial sympathetic denervation and is associated with regional nerve sprouting. The extent of sympathetic remodeling is similar in animals that develop sudden death compared with survivors; this suggests that sympathetic remodeling in hibernating myocardium is not an independent trigger for sudden death. Nevertheless, sympathetic remodeling likely contributes to electrical instability in combination with other factors.
Source: AJP: Heart and Circulatory Physiology - January 15, 2013 Category: Cardiology Authors: Fernandez, S. F., Ovchinnikov, V., Canty, J. M., Fallavollita, J. A. Tags: INTEGRATIVE CARDIOVASCULAR PHYSIOLOGY AND PATHOPHYSIOLOGY Source Type: research

Identification of a region of rat chromosome 1 that impairs the myogenic response and autoregulation of cerebral blood flow in fawn-hooded hypertensive rats
This study examined the effects of transfer of a 2.4-Mbp region of rat chromosome 1 (RNO1) from Brown Norway (BN) into fawn-hooded hypertensive (FHH) rats on autoregulation (AR) of cerebral blood flow (CBF) and the myogenic response of middle cerebral arteries (MCAs). AR of CBF was poor in FHH and FHH.1BN AR– congenic strains that excluded the critical 2.4-Mbp region. In contrast, AR was restored in FHH.1BN AR+ congenic strains that included this region. The diameter of MCAs of FHH rats increased from 140 ± 14 to 157 ± 18 μm when transmural pressure was increased from 40 to 140 mmHg, but it decreased...
Source: AJP: Heart and Circulatory Physiology - January 15, 2013 Category: Cardiology Authors: Pabbidi, M. R., Juncos, J., Juncos, L., Renic, M., Tullos, H. J., Lazar, J., Jacob, H. J., Harder, D. R., Roman, R. J. Tags: INTEGRATIVE CARDIOVASCULAR PHYSIOLOGY AND PATHOPHYSIOLOGY Source Type: research

Effects of intrathecal kynurenate on arterial pressure during chronic osmotic stress in conscious rats
This study investigated whether increased MAP during chronic osmotic stress depends on activation of spinal glutamate receptors. Rats were chronically instrumented with an indwelling intrathecal (i.t.) catheter for antagonist delivery to the spinal cord and a radiotelemetry transmitter for continuous monitoring of MAP and heart rate. Osmotic stress induced by 48 h of water deprivation (WD) increased MAP by ~15 mmHg. Intrathecal kynurenic acid, a nonspecific antagonist of ionotropic glutamate receptors, decreased MAP significantly more after 48 h of WD compared with the water-replete state. Water-deprived rats also showed a...
Source: AJP: Heart and Circulatory Physiology - January 15, 2013 Category: Cardiology Authors: Veitenheimer, B., Osborn, J. W. Tags: CARDIOVASCULAR NEUROHORMONAL REGULATION Source Type: research

Cardiomyocyte-specific overexpression of an active form of Rac predisposes the heart to increased myocardial stunning and ischemia-reperfusion injury
The GTP-binding protein Rac regulates diverse cellular functions including activation of NADPH oxidase, a major source of superoxide production (O2·–). Rac1-mediated NADPH oxidase activation is increased after myocardial infarction (MI) and heart failure both in animals and humans; however, the impact of increased myocardial Rac on impending ischemia-reperfusion (I/R) is unknown. A novel transgenic mouse model with cardiac-specific overexpression of constitutively active mutant form of Zea maize Rac D (ZmRacD) gene has been reported with increased myocardial Rac-GTPase activity and O2·– generation...
Source: AJP: Heart and Circulatory Physiology - January 15, 2013 Category: Cardiology Authors: Talukder, M. A. H., Elnakish, M. T., Yang, F., Nishijima, Y., Alhaj, M. A., Velayutham, M., Hassanain, H. H., Zweier, J. L. Tags: SIGNALING AND STRESS RESPONSE Source Type: research

Macrophage migration inhibitory factor antagonizes pressure overload-induced cardiac hypertrophy
Macrophage migration inhibitory factor (MIF) functions as a proinflammatory cytokine when secreted from the cell, but it also exhibits antioxidant properties by virtue of its intrinsic oxidoreductase activity. Since increased production of ROS is implicated in the development of left ventricular hypertrophy, we hypothesized that the redox activity of MIF protects the myocardium when exposed to hemodynamic stress. In a mouse model of myocardial hypertrophy induced by transverse aortic coarctation (TAC) for 10 days, we showed that growth of the MIF-deficient heart was significantly greater by 32% compared with wild-type (WT)...
Source: AJP: Heart and Circulatory Physiology - January 15, 2013 Category: Cardiology Authors: Koga, K., Kenessey, A., Ojamaa, K. Tags: SIGNALING AND STRESS RESPONSE Source Type: research

MAP kinase kinase kinase-2 (MEKK2) regulates hypertrophic remodeling of the right ventricle in hypoxia-induced pulmonary hypertension
In conclusion, signaling by MEKK2 contributes to RV hypertrophy and altered myocardial inflammatory gene expression in response to hypoxia-induced PH. Therapies targeting MEKK2 may protect the myocardium from hypertrophy and pathological remodeling in human PH.
Source: AJP: Heart and Circulatory Physiology - January 15, 2013 Category: Cardiology Authors: Brown, R. D., Ambler, S. K., Li, M., Sullivan, T. M., Henry, L. N., Crossno, J. T., Long, C. S., Garrington, T. P., Stenmark, K. R. Tags: SIGNALING AND STRESS RESPONSE Source Type: research

Impact of site-specific phosphorylation of protein kinase A sites Ser23 and Ser24 of cardiac troponin I in human cardiomyocytes
PKA-mediated phosphorylation of contractile proteins upon β-adrenergic stimulation plays an important role in the regulation of cardiac performance. Phosphorylation of the PKA sites (Ser23/Ser24) of cardiac troponin (cTn)I results in a decrease in myofilament Ca2+ sensitivity and an increase in the rate of relaxation. However, the relation between the level of phosphorylation of the sites and the functional effects in the human myocardium is unknown. Therefore, site-directed mutagenesis was used to study the effects of phosphorylation at Ser23 and Ser24 of cTnI on myofilament function in human cardiac tissue. Serines ...
Source: AJP: Heart and Circulatory Physiology - January 15, 2013 Category: Cardiology Authors: Wijnker, P. J. M., Foster, D. B., Tsao, A. L., Frazier, A. H., dos Remedios, C. G., Murphy, A. M., Stienen, G. J. M., van der Velden, J. Tags: MUSCLE MECHANICS AND VENTRICULAR FUNCTION Source Type: research

Deletion of 1-43 amino acids in cardiac myosin essential light chain blunts length dependency of Ca2+ sensitivity and cross-bridge detachment kinetics
The role of cardiac myosin essential light chain (ELC) in the sarcomere length (SL) dependency of myofilament contractility is unknown. Therefore, mechanical and dynamic contractile properties were measured at SL 1.9 and 2.2 μm in cardiac muscle fibers from two groups of transgenic (Tg) mice: 1) Tg-wild-type (WT) mice that expressed WT human ventricular ELC and 2) Tg-43 mice that expressed a mutant ELC lacking 1–43 amino acids. In agreement with previous studies, Ca2+-activated maximal tension decreased significantly in Tg-43 fibers. pCa50 (–log10 [Ca2+]free required for half maximal activation) values at SL...
Source: AJP: Heart and Circulatory Physiology - January 15, 2013 Category: Cardiology Authors: Michael, J. J., Gollapudi, S. K., Ford, S. J., Kazmierczak, K., Szczesna-Cordary, D., Chandra, M. Tags: MUSCLE MECHANICS AND VENTRICULAR FUNCTION Source Type: research

Cardiomyocyte architectural plasticity in fetal, neonatal, and adult pig hearts delineated with diffusion tensor MRI
Cardiomyocyte organization is a critical determinant of coordinated cardiac contractile function. Because of the acute opening of the pulmonary circulation, the relative workload of the left ventricle (LV) and right ventricle (RV) changes substantially immediately after birth. We hypothesized that three-dimensional cardiomyocyte architecture might be required to adapt rapidly to accommodate programmed perinatal changes of cardiac function. Isolated fixed hearts from pig fetuses or pigs at midgestation, preborn, postnatal day 1 (P1), postnatal day 5, postnatal day 14 (P14), and adulthood (n = 5 for each group) were acquired...
Source: AJP: Heart and Circulatory Physiology - January 15, 2013 Category: Cardiology Authors: Zhang, L., Allen, J., Hu, L., Caruthers, S. D., Wickline, S. A., Chen, J. Tags: MUSCLE MECHANICS AND VENTRICULAR FUNCTION Source Type: research

An angiogenesis model for investigating multicellular interactions across intact microvascular networks
The objective of this study was to develop an angiogenesis model that enables probing of multicellular and multisystem interactions at the molecular level across an intact adult microvascular network. Adult male Wistar rat mesenteric windows were aseptically harvested and cultured in serum-free minimum essential media. Viability/cytotoxicity analysis revealed that cells remain alive for at least 7 days. Immunohistochemical labeling at 3 days for platelet endothelial cell adhesion molecule (PECAM), neuron-glial antigen 2 (NG2), lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1), and class III β-tubulin identif...
Source: AJP: Heart and Circulatory Physiology - January 15, 2013 Category: Cardiology Authors: Stapor, P. C., Azimi, M. S., Ahsan, T., Murfee, W. L. Tags: VASCULAR BIOLOGY AND MICROCIRCULATION Source Type: research

Artery wall layer dimensions during normal pregnancy: a longitudinal study using noninvasive high-frequency ultrasound
The vascular effects of normal pregnancy were investigated by estimating the intima and media thicknesses of the common carotid artery separately using 22-MHz ultrasound (Collagenoson, Meudt, Germany) in 57 healthy women with normal pregnancies and pregnancy outcomes, in all three trimesters and at 1 yr postpartum. A thick intima, thin media, and high intima-to-media (I/M) ratio are signs of a less healthy artery wall. Mean artery wall layer dimensions remained fairly constant during pregnancy, but the intima thickness and I/M thickness ratio appeared to improve (decrease) postpartum (P < 0.001 for both). The cardiovasc...
Source: AJP: Heart and Circulatory Physiology - January 15, 2013 Category: Cardiology Authors: Akhter, T., Larsson, A., Larsson, M., Wikstrom, A.-K., Naessen, T. Tags: VASCULAR BIOLOGY AND MICROCIRCULATION Source Type: research

Streptozotocin-induced diabetes differentially affects sympathetic innervation and control of plantar metatarsal and mesenteric arteries in the rat
In humans neural control of arterial vessels supplying skin in the extremities is particularly vulnerable to the effects of diabetes. Here the streptozotocin (STZ) rat model of type 1 diabetes was used to compare effects on neurovascular function in plantar metatarsal arteries (PMAs), which supply blood to skin of hind paw digits, with those in mesenteric arteries (MAs). Twelve weeks after STZ (60 mg/kg ip), wire myography was used to assess vascular function. In PMAs, lumen dimensions were unchanged but both nerve-evoked contractions and sensitivity to α1 (phenylephrine, methoxamine)- and α2 (clonidine)-adreno...
Source: AJP: Heart and Circulatory Physiology - January 15, 2013 Category: Cardiology Authors: Johansen, N. J., Tripovic, D., Brock, J. A. Tags: VASCULAR BIOLOGY AND MICROCIRCULATION Source Type: research

(-)-Epicatechin administration and exercising skeletal muscle vascular control and microvascular oxygenation in healthy rats
Consumption of the dietary flavanol (–)-epicatechin (EPI) is associated with enhanced endothelial function and augmented skeletal muscle capillarity and mitochondrial volume density. The potential for EPI to improve peripheral vascular function and muscle oxygenation during exercise is unknown. We tested the hypothesis that EPI administration in healthy rats would improve treadmill exercise performance secondary to elevated skeletal muscle blood flow and vascular conductance [VC, blood flow/mean arterial pressure (MAP)] and improved skeletal muscle microvascular oxygenation. Rats received water (control, n = 12) or 4...
Source: AJP: Heart and Circulatory Physiology - January 15, 2013 Category: Cardiology Authors: Copp, S. W., Inagaki, T., White, M. J., Hirai, D. M., Ferguson, S. K., Holdsworth, C. T., Sims, G. E., Poole, D. C., Musch, T. I. Tags: VASCULAR BIOLOGY AND MICROCIRCULATION Source Type: research

Chronic hypoxia decreases arterial and venous compliance in isolated perfused rat lungs: an effect that is reversed by exogenous L-arginine
Chronic hypoxia (CH)-induced pulmonary hypertension is characterized by vasoconstriction and vascular remodeling, leading to right ventricular dysfunction. Given the role of arterial compliance (Ca) in right ventricular work, a decrease in Ca would add to right ventricular work. Nitric oxide (NO) is a potent vasodilator made by NO synthases from l-arginine (l-Arg). However, little is known of the effect of l-Arg on vascular compliance (Cv) in the lung. We hypothesized that exposure to CH would decrease Ca and that this effect would be reversed by exogenous l-Arg. Sprague-Dawley rats were exposed to either normoxia or CH fo...
Source: AJP: Heart and Circulatory Physiology - January 15, 2013 Category: Cardiology Authors: Jin, Y., Chen, B., Calvert, T. J., Chicoine, L. G., Liu, Y., Nelin, L. D. Tags: VASCULAR BIOLOGY AND MICROCIRCULATION Source Type: research

Vascular dysfunction in young, mid-aged and aged mice with latent cytomegalovirus infections
Human cytomegalovirus (HCMV) is associated with vascular diseases in both immunosuppressed and immunocompetent individuals. CMV infections cycle between active and latent phases throughout life. We and others have shown vascular dysfunction during active mouse CMV (mCMV) infections. Few studies have examined changes in physiology during latent CMV infections, particularly vascular responses or whether the negative effects of aging on vascular function and fertility will be exacerbated under these conditions. We measured vascular responses in intact mesenteric and uterine arteries dissected from young, mid-aged, and aged la...
Source: AJP: Heart and Circulatory Physiology - January 15, 2013 Category: Cardiology Authors: Gombos, R. B., Brown, J. C., Teefy, J., Gibeault, R. L., Conn, K. L., Schang, L. M., Hemmings, D. G. Tags: VASCULAR BIOLOGY AND MICROCIRCULATION Source Type: research

The Anrep effect: 100 years later
Myocardial stretch elicits a rapid increase in developed force, which is mainly caused by an increase in myofilament calcium sensitivity (Frank-Starling mechanism). Over the ensuing 10–15 min, a second gradual increase in force takes place. This slow force response to stretch is known to be the result of an increase in the calcium transient amplitude and constitutes the in vitro equivalent of the Anrep effect described 100 years ago in the intact heart. In the present review, we will update and discuss what is known about the Anrep effect as the mechanical counterpart of autocrine/paracrine mechanisms involved in its...
Source: AJP: Heart and Circulatory Physiology - January 15, 2013 Category: Cardiology Authors: Cingolani, H. E., Perez, N. G., Cingolani, O. H., Ennis, I. L. Tags: REVIEW Source Type: research

Role of protein kinase C-{alpha} in hypertonicity-stimulated urea permeability in mouse inner medullary collecting ducts
The kidney's ability to concentrate urine is vitally important to our quality of life. In the hypertonic environment of the kidney, urea transporters must be regulated to optimize function. We previously showed that hypertonicity increases urea permeability and that the protein kinase C (PKC) blockers chelerythrine and rottlerin decreased hypertonicity-stimulated urea permeability in rat inner medullary collecting ducts (IMCDs). Because PKCα knockout (PKCα–/–) mice have a urine-concentrating defect, we tested the effect of hypertonicity on urea permeability in isolated perfused mouse IMCDs. Increasi...
Source: AJP: Renal Physiology - January 15, 2013 Category: Urology & Nephrology Authors: Wang, Y., Klein, J. D., Froehlich, O., Sands, J. M. Tags: ARTICLES Source Type: research