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

Authors

  • L. Chen
  • M. Kaßmann
  • M. Sendeski
  • D. Tsvetkov
  • L. Marko
  • L. Michalick
  • M. Riehle
  • L.B. Wolfgang
  • K.M. Wolfgang
  • C. Harteneck
  • M. Tepel
  • A. Patzak
  • M. Gollasch

Journal

  • Acta Physiologica

Citation

  • Acta Physiol 213 (2): 481-491

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.


DOI

doi:10.1111/apha.12355