SKA-31, an activator of endothelial Ca2+ -activated K+ channels evokes robust vasodilation in rat mesenteric arteries

European Journal of Pharmacology
Rayan Khaddaj-MallatAndrew P Braun

Abstract

It is now well recognized that endothelial KCa2.3 and KCa3.1 channel activities contribute to dilation of resistance arteries via endothelium-mediated hyperpolarization and vascular smooth muscle relaxation. In this study, we have investigated the functional effect of the KCa channel activator SKA-31 in third order rat mesenteric arteries using arterial pressure myography. Isolated arteries were cannulated, pressurized intraluminally to 70 mmHg at 36 °C and then constricted with 1 μM phenylephrine. Acute bath exposure to SKA-31 evoked a robust and reversible inhibition of developed tone (IC50 = 0.22 μM). The vasodilatory effects of SKA-31 and acetylcholine were blunted in the presence of KCa2.3 and KCa3.1 channel antagonists, and were largely prevented following endothelial denudation. Western blot and q-PCR analyses of isolated mesenteric arteries revealed KCa2.3 and KCa3.1 channel expression at the protein and mRNA levels, respectively. Penitrem-A, an inhibitor of KCa1.1 channels, decreased vasodilatory responses to acetylcholine, sodium nitroprusside and NS-1619, but had little effect on SKA-31. Similarly, bath exposure to the eNOS inhibitor L-NAME did not alter SKA-31 and acetylcholine-mediated vasodilation. Collectively, t...Continue Reading

Citations

Sep 6, 2019·Current Medicinal Chemistry·Francesco MocciaRoberto Berra-Romani
May 30, 2020·American Journal of Physiology. Heart and Circulatory Physiology·Sheila Flavahan, Nicholas A Flavahan
Jul 19, 2019·International Journal of Molecular Sciences·Rayan Khaddaj MallatAndrew P Braun
Aug 28, 2019·International Journal of Molecular Sciences·Monika KlozaHanna Kozłowska

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