Suppression of K +-induced hyperpolarization by phenylephrine in rat mesenteric artery: Relevance to studies of endothelium-derived hyperpolarizing factor

Abstract

In intact mesenteric arteries, increasing [K +] o by 5 mM hyperpolarized both endothelial and smooth muscle cells. Subsequent exposure to 10 μM phenylephrine depolarized both cell types which were then repolarized by a 5 mM increase in [K +] o. In endothelium-denuded vessels, increasing [K +] o by 5 mM hyperpolarized the smooth muscle but K + had no effect after depolarization by 10 μM phenylephrine. On subsequent exposure to iberiotoxin plus 4-aminopyridine, the repolarizing action of 5 mM K + was restored. In endothelium-intact vessels exposed to phenylephrine, pretreatment with a gap junction inhibitor (gap 27) reduced K +-mediated smooth muscle repolarization without affecting the endothelial cell response. It is concluded that phenylephrine-induced efflux of K + via smooth muscle K + channels produces a local increase in [K +] o which impairs repolarization to added K +. Thus, studies involving vessels precontracted with agonists which increase [K +] o maximize the role of gap junctions and minimize any contribution to the EDHF pathway from endothelium-derived K +.