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⁺. British Journal of Pharmacology (2001) 134, 1–5; doi:10.1038/sj.bjp.0704256