Proceedings of The Physiological Society

Europhysiology 2018 (London, UK) (2018) Proc Physiol Soc 41, PCA369

Poster Communications

Organotypic expression of vascular smooth muscle Kv7.1 channels - potential for renoprotection?

R. Schubert1, A. Bachmann1, F. Stocker1, P. Quinn1, S. Braun1, C. Kammermeier2, A. Kannt2, N. Schmidt1

1. Cardiovascular Physiology, Medical Faculty Mannheim, University Heidelberg, Mannheim, Germany. 2. Sanofi Diabetes Research, Frankfurt, Germany.

Introduction: Blood flow regulation depends on the contractile properties of vascular smooth muscle. The latter is controlled largely by voltage-gated potassium (Kv) channels, especially Kv7 channels. Vascular smooth muscle expresses mainly Kv7.1, Kv7.4 and Kv7.5 channels. Kv7.1 channels are expressed only in a few vessels, in particular in renal arteries. Therefore, this study addressed the hypothesis that Kv7.1 channels contribute to the regulation of the contractility of renal arteries. Methods: Renal segmental arteries of Wistar rats were studied using real-time qPCR and isometric myography. Intact kidneys were explored using constant flow perfusion. Results: In renal segmental arteries, mRNA expression of Kv7.1 channels was larger than that of Kv7.4 and Kv7.5 channels. The Kv7.1 channel opener R-L3 (L-364,373) reduced methoxamine-induced contractions of isolated renal segmental arteries in a concentration dependent manner. At moderate concentrations of R-L3, its effect was abolished completely by HMR1556, a selective Kv7.1 channel blocker. HMR1556 alone was without effect on methoxamine-induced contraction. Further, HMR1556 did not affect the anticontractile effect of the cGMP-coupled vasodilator ANP and the cAMP-coupled vasodilator urocortin. Notably, the effect of ANP and urocortin were the same in the absence and the presence of R-L3. In addition, R-L3 reduced methoxamine-induced perfusion pressure in intact perfused kidneys. This effect was attenuated considerably by HMR1556. HMR1556 alone was without effect on methoxamine-induced perfusion pressure. Urocortin reduced methoxamine-induced perfusion pressure. This, effect was the same in the absence and the presence of R-L3. Conclusions: The results show that Kv7.1 channels are expressed in rat renal segmental arteries, but do not contribute to MX-induced contraction or ANP- and urocortin-induced relaxation. After pharmacological activation, Kv7.1 channels reduce basal tone and basal perfusion pressure, but leave MX-induced contraction as well as ANP- and urocortin-induced relaxation intact. Thus, Kv7.1 channel activation improves renal perfusion without altering vasoconstrictor- or vasodilator-evoked regulation suggesting that these channels may serve as targets for renoprotection.

Where applicable, experiments conform with Society ethical requirements