Key role of Ca2+‐activated K+ channels of small and intermediate conductance in the NO signaling of resistance vessels

Abstract

Ca2+‐activated K+ channels (KCa) and nitric oxide (NO) play a central role in the control of vasomotor tone in resistance arteries. To evaluate the contribution of KCa channels to NO‐mediated dilation, we analyzed the vasomotor responses and NO production (chemiluminiscence) induced by the endothelium‐dependent vasodilator, acetylcholine (ACh), or the Ca2+ ionophore, ionomycin, in isolated arterial mesenteric bed of rat. ACh (0.01–10μM) elicited a concentration‐dependent vasodilatation. In phenylephrine‐contracted mesenteries, NO synthase (NOS) inhibition with Nω‐nitro‐L‐arginine (L‐NA) reduced the response to ACh. Blockade of KCa channels with tetraethylammonium (TEA) or inward rectifier K+ channels with Ba2+ blunted the response to ACh. L‐NA inhibited the ACh‐induced relaxation in presence of Ba2+, but not TEA. In addition, TEA blocked the NO production induced by ACh. In KCl‐contracted vessels, the relaxation‐elicited by ACh or 1μM ionomycin was abolished by L‐NA and inhibited by TEA or simultaneous blockade of KCa channels of small (SKCa) and intermediate (IKCa) conductance with apamin and TRAM‐34, respectively. Apamin and TRAM‐34 also abolished the NO production activated by 100nM ACh. These results indicate that functional SKCa and IKCa channels are required for Ca2+‐mediated eNOS activation. Membrane hyperpolarization is not involved in the regulation of NO production by these channels.VRAID 15/2009