Functional transient receptor potential vanilloid 1 and transient receptor potential vanilloid 4 channels along different segments of the renal vasculature

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Item Type:	Article
Title:	Functional transient receptor potential vanilloid 1 and transient receptor potential vanilloid 4 channels along different segments of the renal vasculature
Creators Name:	Chen, L., Kaßmann, M., Sendeski, M., Tsvetkov, D., Marko, L., Michalick, L., Riehle, M., Wolfgang, L.B., Wolfgang, K.M., Harteneck, C., Tepel, M., Patzak, A. and Gollasch, M.
Abstract:	AIM: Transient receptor potential vanilloid 1 (TRPV1) and vanilloid 4 (TRPV4) cation channels have been recently identified to promote endothelium-dependent relaxation of mouse mesenteric arteries. However, the role TRPV1 and TRPV4 in the renal vasculature is largely unknown. We hypothesized that TRPV1/4 play a role in endothelium-dependent vasodilation of renal blood vessels. METHODS: We studied the distribution of functional TRPV1/4 along different segments of the renal vasculature. Mesenteric arteries were studied as control vessels. RESULTS: The TRPV1 agonist capsaicin relaxed mouse mesenteric arteries with an EC50 of 25 nM, but large mouse renal arteries or rat descending vasa recta only at >100-fold higher concentrations. The vasodilatory effect of capsaicin in the low-nanomolar concentration range was endothelium-dependent and absent in vessels of Trpv1 -/- mice. The TRPV4 agonist GSK1016790A relaxed large conducting renal arteries, mesenteric arteries and vasa recta with EC50 of 18 nM, 63 nM and ~10 nM, respectively. These effects were endothelium-dependent and inhibited by a TRPV4 antagonist, AB159908 (10 muM). Capsaicin and GSK1016790A produced vascular dilation in isolated mouse perfused kidneys with EC50 of 23 nM and 3 nM, respectively. The capsaicin effects were largely reduced in Trpv1 -/- kidneys and the effects of GSK1016790A were inhibited in Trpv4 -/- kidneys. CONCLUSION: Our results demonstrate that two TRPV channels have unique sites of vasoregulatory function in the kidney with functional TRPV1 having a narrow, discrete distribution in the resistance vasculature and TRPV4 having more universal, widespread distribution along different vascular segments. We suggest that TRPV1/4 channels are potent therapeutic targets for site-specific vasodilation in the kidney.
Keywords:	Endothelial Relaxation, Medullary Blood Flow, Renal Arterial Resistance, Renal Endothelium, TRPV1 Channels, TRPV4 Channels, Vasa Recta, Animals, Rats, Mice
Source:	Acta Physiologica
ISSN:	1748-1708
Publisher:	Wiley-Blackwell
Volume:	213
Number:	2
Page Range:	481-491
Date:	February 2015
Official Publication:	https://doi.org/10.1111/apha.12355
PubMed:	View item in PubMed

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