Suppression Of K+-Induced Hyperpolarization By Phenylephrine In Rat Mesenteric Artery: Relevance To Studies Of Endothelium-Derived Hyperpolarizing Factor

In intact mesenteric arteries. increasing [K+](o) by 5 mm hyperpolarized both endothelial and smooth muscle cells. Subsequent exposure to 10 muM phenylephrine depolarized both cell types which were then repolarized by a 5 mm increase in [K+](o) In endothelium-denuded vessels, incieasing [K+](o) by 5 mM hyperpolarized the smooth muscle but K+ had no effect after depolarization by 10 pm 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+ ria 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+.