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http://dx.doi.org/10.1212/wnl.10.2.123 | DOI Listing |
Int J Mol Sci
November 2021
Department of Nephrology, Radboud Institute for Molecular Life Sciences (RIMLS), Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands.
Increased expression and activity of the Ca channel transient receptor potential channel 6 (TRPC6) is associated with focal segmental glomerulosclerosis, but therapeutic strategies to target TRPC6 are currently lacking. Nitric oxide (NO) is crucial for normal glomerular function and plays a protective role in preventing glomerular diseases. We investigated if NO prevents podocyte injury by inhibiting injurious TRPC6-mediated signaling in a soluble guanylate cyclase (sGC)-dependent manner and studied the therapeutic potential of the sGC stimulator Riociguat.
View Article and Find Full Text PDFAm J Physiol Renal Physiol
March 2018
Division of Nephrology, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland.
tested whether rat descending vasa recta (DVR) undergo regulatory adaptations after the kidney is exposed to ischemia. Left kidneys (LK) were subjected to 30-min renal artery cross clamp. After 48 h, the postischemic LK and contralateral right kidney (RK) were harvested for study.
View Article and Find Full Text PDFAm J Physiol Renal Physiol
June 2014
Division of Nephrology, Duke University Medical Center, Durham, North Carolina; Center for Human Genetics, Duke University Medical Center, Durham, North Carolina;
The emerging role of the transient receptor potential cation channel isotype 6 (TRPC6) as a central contributor to various pathological processes affecting podocytes has generated interest in the development of therapeutics to modulate its function. Recent insights into the regulation of TRPC6 have revealed PKG as a potent negative modulator of TRPC6 conductance and associated signaling via its phosphorylation at two highly conserved amino acid residues: Thr(69)/Thr(70) (Thr(69) in mice and Thr(70) in humans) and Ser(321)/Ser(322) (Ser(321) in mice and Ser(322) in humans). Here, we tested the role of PKG in modulating TRPC6-dependent responses in primary and conditionally immortalized mouse podocytes.
View Article and Find Full Text PDFAm J Physiol Renal Physiol
December 2012
Dept. of Medicine, Univ. of Virginia Health Sciences Center, Charlottesville, VA 22908-1409, USA.
Effects of low salt (LS) on (pro)renin receptor (PRR) expression are not well established. We hypothesized that LS enhances renal PRR expression via the cGMP-protein kinase G (PKG) signaling pathway. Sprague-Dawley rats were fed a normal-salt (NS) or LS diet associated with intrarenal cortical administration of vehicle (V), the nitric oxide (NO) synthase inhibitor nitro-l-arginine methyl ester (l-NAME), the NO donor S-nitroso-N-acetyl-dl-penicillamine (SNAP), the cGMP analog 8-bromoguanosine (8-Br)-cGMP, the guanylyl cyclase inhibitor 1H-[1, 2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), or a PKG inhibitor (PKGi) for 6 days via osmotic minipump.
View Article and Find Full Text PDFAm J Physiol Renal Physiol
August 2009
Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA.
Nitric oxide (NO), a neurotransmitter in the lower urinary tract, stimulates soluble guanylyl cyclase (sGC) and in turn cGMP-dependent protein kinase G (PKG) to modulate a number of downstream targets. NO donors reduce bladder hyperactivity in some pathological models but do not affect normal bladder activity in the adult rat. In this study, the NO donor S-nitroso-N-acetyl-DL-penicillamine (SNAP; 100 microM) decreased the amplitude and frequency of spontaneous and carbachol-enhanced contractions in neonatal rat bladder strips, which are intrinsically hyperactive.
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