Evaluating the voiding spot assay in mice: a simple method with complex environmental interactions
The voiding spot assay (VSA) on filter paper is an increasingly popular method for studying lower urinary tract physiology in mice. However, the ways VSAs are performed differ significantly between laboratories, and many variables are introduced compared with the mouse’s normal housing situation. Rodents are intelligent social animals, and it is increasingly understood that social and environmental stresses have significant effects on their physiology. Surprisingly, little is known about whether change of environment during VSA affects mouse voiding and what the best methodologies are for retaining "natural" micturit...
Source: AJP: Renal Physiology - December 6, 2017 Category: Urology & Nephrology Authors: Chen, H., Zhang, L., Hill, W. G., Yu, W. Tags: RESEARCH ARTICLE Source Type: research

Angiotensin II type 1a receptor-deficient mice develop angiotensin II-induced oxidative stress and DNA damage without blood pressure increase
Hypertensive patients have an increased risk of developing kidney cancer. We have shown in vivo that besides elevating blood pressure, angiotensin II causes DNA damage dose dependently. Here, the role of blood pressure in the formation of DNA damage is studied. Mice lacking one of the two murine angiotensin II type 1 receptor (AT1R) subtypes, AT1aR, were equipped with osmotic minipumps, delivering angiotensin II during 28 days. Parameters of oxidative stress and DNA damage of kidneys and hearts of AT1aR-knockout mice were compared with wild-type (C57BL/6) mice receiving angiotensin II, and additionally, with wild-type mice...
Source: AJP: Renal Physiology - December 6, 2017 Category: Urology & Nephrology Authors: Zimnol, A., Amann, K., Mandel, P., Hartmann, C., Schupp, N. Tags: RESEARCH ARTICLE Source Type: research

Versatility of NaCl transport mechanisms in the cortical collecting duct
The cortical collecting duct (CCD) forms part of the aldosterone-sensitive distal nephron and plays an essential role in maintaining the NaCl balance and acid-base status. The CCD epithelium comprises principal cells as well as different types of intercalated cells. Until recently, transcellular Na+ transport was thought to be restricted to principal cells, whereas (acid-secreting) type A and (bicarbonate-secreting) type B intercalated cells were associated with the regulation of acid-base homeostasis. This review describes how this traditional view has been upended by several discoveries in the past decade. A series of st...
Source: AJP: Renal Physiology - December 6, 2017 Category: Urology & Nephrology Authors: Edwards, A., Crambert, G. Tags: REVIEW Source Type: research

Collecting duct prorenin receptor knockout reduces renal function, increases sodium excretion, and mitigates renal responses in ANG II-induced hypertensive mice
Augmented intratubular angiotensin (ANG) II is a key determinant of enhanced distal Na+ reabsorption via activation of epithelial Na+ channels (ENaC) and other transporters, which leads to the development of high blood pressure (BP). In ANG II-induced hypertension, there is increased expression of the prorenin receptor (PRR) in the collecting duct (CD), which has been implicated in the stimulation of the sodium transporters and resultant hypertension. The impact of PRR deletion along the nephron on BP regulation and Na+ handling remains controversial. In the present study, we investigate the role of PRR in the regulation o...
Source: AJP: Renal Physiology - December 1, 2017 Category: Urology & Nephrology Authors: Prieto, M. C., Reverte, V., Mamenko, M., Kuczeriszka, M., Veiras, L. C., Rosales, C. B., McLellan, M., Gentile, O., Jensen, V. B., Ichihara, A., McDonough, A. A., Pochynyuk, O. M., Gonzalez, A. A. Tags: RESEARCH ARTICLE Source Type: research

Glomerular mesangial cell recruitment and function require the co-receptor neuropilin-1
Proteinuria has been reported in cancer patients receiving agents that target the transmembrane receptor neuropilin-1 (Nrp1) suggesting potential adverse effects on glomerular function. Here we show that Nrp1 is highly expressed by mesangial cells and that genetic deletion of the Nrp1 gene from PDGF receptor-β+ mesangial cells results in proteinuric disease and glomerulosclerosis, leading to renal failure and death within 6 wk of age in mice. The major defect is a failure of mesangial cell migration that is required to establish the mature glomerular tuft. In vitro data show that the potent chemotactic effect of PDGFB...
Source: AJP: Renal Physiology - December 1, 2017 Category: Urology & Nephrology Authors: Bartlett, C. S., Scott, R. P., Carota, I. A., Wnuk, M. L., Kanwar, Y. S., Miner, J. H., Quaggin, S. E. Tags: RESEARCH ARTICLE Source Type: research

Aberrant Smad3 phosphoisoforms in cyst-lining epithelial cells in the cpk mouse, a model of autosomal recessive polycystic kidney disease
In conclusion, a qualitative rather than a quantitative abnormality of the TGF-β/Smad3 pathway is involved in PKD and may be a target for disease-specific intervention. (Source: AJP: Renal Physiology)
Source: AJP: Renal Physiology - December 1, 2017 Category: Urology & Nephrology Authors: Hama, T., Nakanishi, K., Sato, M., Mukaiyama, H., Togawa, H., Shima, Y., Miyajima, M., Nozu, K., Nagao, S., Takahashi, H., Sako, M., Iijima, K., Yoshikawa, N., Suzuki, H. Tags: RESEARCH ARTICLE Source Type: research

Adenosine A1 receptor-operated calcium entry in renal afferent arterioles is dependent on postnatal maturation of TRPC3 channels
In this study, we show that selective activation of A1Rs by 2-chloro-N6-cyclopentyladenosine (CCPA) does not stimulate store-operated Ca2+ entry in afferent arterioles isolated from neonatal pigs. However, CCPA-induced [Ca2+]i elevation is dependent on phospholipase C and transient receptor potential cation channel, subfamily C, member 3 (TRPC3). Basal [Ca2+]i was unchanged in afferent arterioles isolated from newborn (0-day-old) pigs compared with their 20-day-old counterparts. By contrast, CCPA treatment resulted in significantly larger [Ca2+]i in afferent arterioles from 20-day-old pigs. A1R protein expression levels in...
Source: AJP: Renal Physiology - December 1, 2017 Category: Urology & Nephrology Authors: Soni, H., Peixoto-Neves, D., Buddington, R. K., Adebiyi, A. Tags: RESEARCH ARTICLE Source Type: research

Effect of salt intake on afferent arteriolar dilatation: role of connecting tubule glomerular feedback (CTGF)
Afferent arteriole (Af-Art) resistance is modulated by two intrinsic nephron feedbacks: 1) the vasoconstrictor tubuloglomerular feedback (TGF) mediated by Na+-K+-2Cl– cotransporters (NKCC2) in the macula densa and blocked by furosemide and 2) the vasodilator connecting tubule glomerular feedback (CTGF), mediated by epithelial Na+ channels (ENaC) in the connecting tubule and blocked by benzamil. High salt intake reduces Af-Art vasoconstrictor ability in Dahl salt-sensitive rats (Dahl SS). Previously, we measured CTGF indirectly, by differences between TGF responses with and without CTGF inhibition. We recently develop...
Source: AJP: Renal Physiology - December 1, 2017 Category: Urology & Nephrology Authors: Wang, H., Romero, C. A., Masjoan Juncos, J. X., Monu, S. R., Peterson, E. L., Carretero, O. A. Tags: RESEARCH ARTICLE Source Type: research

All-trans-retinoic acid-mediated cytoprotection in LLC-PK1 renal epithelial cells is coupled to p-ERK activation in a ROS-independent manner
Although all-trans-retinoic acid (ATRA) provides protection against a variety of conditions in vivo, particularly ischemia, the molecular mechanisms underpinning these effects remain unclear. The present studies were designed to assess potential mechanisms by which ATRA affords cytoprotection against renal toxicants in LLC-PK1 cells. Pretreatment of LLC-PK1 cells with ATRA (25 μM) for 24 h afforded cytoprotection against oncotic cell death induced by p-aminophenol (PAP), 2-(glutathion-S-yl)hydroquinone (MGHQ), and iodoacetamide but not against apoptotic cell death induced by cisplatin. Inhibition of protein synthesis wi...
Source: AJP: Renal Physiology - December 1, 2017 Category: Urology & Nephrology Authors: Sapiro, J. M., Monks, T. J., Lau, S. S. Tags: RESEARCH ARTICLE Source Type: research

Coupling between phosphate and calcium homeostasis: a mathematical model
We developed a mathematical model of calcium (Ca) and phosphate (PO4) homeostasis in the rat to elucidate the hormonal mechanisms that underlie the regulation of Ca and PO4 balance. The model represents the exchanges of Ca and PO4 between the intestine, plasma, kidneys, bone, and the intracellular compartment, and the formation of Ca-PO4-fetuin-A complexes. It accounts for the regulation of these fluxes by parathyroid hormone (PTH), vitamin D3, fibroblast growth factor 23, and Ca2+-sensing receptors. Our results suggest that the Ca and PO4 homeostatic systems are robust enough to handle small perturbations in the productio...
Source: AJP: Renal Physiology - December 1, 2017 Category: Urology & Nephrology Authors: Granjon, D., Bonny, O., Edwards, A. Tags: RESEARCH ARTICLE Source Type: research

Special K: once the fun is over an EMT arrives for the bladder
(Source: AJP: Renal Physiology)
Source: AJP: Renal Physiology - December 1, 2017 Category: Urology & Nephrology Authors: Hill, W. G., Yu, W. Tags: EDITORIAL FOCUS Source Type: research

Corrigendum
(Source: AJP: Renal Physiology)
Source: AJP: Renal Physiology - November 29, 2017 Category: Urology & Nephrology Tags: CORRIGENDA Source Type: research

OAB without an overactive bladder in the acute prostaglandin E2 rat model
Intravesical prostaglandin E2 (PGE2) was previously used to induce overactive bladder (OAB) symptoms, as it reduces bladder capacity in rats and causes a "strong urgency sensation" in healthy women. However, the mechanism by which this occurs is unclear. To clarify how PGE2 reduces bladder capacity, 100 µM PGE2 was administered intravesically during open, single-fill cystometry with simultaneous measurement of sphincter EMG in the urethane-anesthetized female Wistar rat. PGE2 was also applied to the urethra or bladder selectively by use of a ligature at the bladder neck before (urethra) or during (bladder) closed-out...
Source: AJP: Renal Physiology - November 29, 2017 Category: Urology & Nephrology Authors: Hokanson, J. A., Langdale, C. L., Sridhar, A., Grill, W. M. Tags: RESEARCH ARTICLE Source Type: research

An excitatory reflex from the superficial peroneal nerve to the bladder in cats
This study in α-chloralose-anesthetized cats discovered an excitatory peroneal nerve-to-bladder reflex. A urethral catheter was used to infuse the bladder with saline and record bladder pressure changes. Electrical stimulation was applied to the superficial peroneal nerve to trigger reflex bladder activity. With the bladder distended at a volume ~90% of bladder capacity, superficial peroneal nerve stimulation (PNS) at 1–3 Hz and threshold (T) intensity for inducing muscle twitching on the posterior thigh induced large-amplitude (40–150 cmH2O) bladder contractions. PNS (1–3 Hz, 1–2T) applied du...
Source: AJP: Renal Physiology - November 29, 2017 Category: Urology & Nephrology Authors: Yu, M., Uy, J., Jiang, X., Li, X., Jones, C., Shen, B., Wang, J., Roppolo, J. R., de Groat, W. C., Tai, C. Tags: RESEARCH ARTICLE Source Type: research

Preventative effects of a HIF inhibitor, 17-DMAG, on partial bladder outlet obstruction-induced bladder dysfunction
Posterior urethral valves are the most common cause of partial bladder outlet obstruction (PBOO) in the pediatric population. Pathological changes in the bladder developed during PBOO are responsible for long-lasting voiding dysfunction in this population despite early surgical interventions. Increasing evidence showed PBOO induces an upregulation of hypoxia-inducible factors (HIFs) and their transcriptional target genes, and they play a role in pathophysiological changes in the obstructed bladders. We hypothesized that blocking HIF pathways can prevent PBOO-induced bladder dysfunction. PBOO was surgically created by ligat...
Source: AJP: Renal Physiology - November 29, 2017 Category: Urology & Nephrology Authors: Iguchi, N., Dönmez, M. I., Malykhina, A. P., Carrasco, A., Wilcox, D. T. Tags: RESEARCH ARTICLE Source Type: research