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 bo th endothelial and smooth muscle cells. Subsequent exposure to 10 muM pheny lephrine 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 depolarizat ion by 10 pm phenylephrine. On subsequent exposure to iberiotoxin plus 4-am inopyridine, the repolarizing action of 5 mm K+ was restored. In endotheliu m-intact vessels exposed to phenylephrine. pretreatment with a gap junction inhibitor (gap 27) reduced K+-mediated smooth muscle repolarization withou t affecting the endothelial cell response. It is concluded that phenylephri ne-induced efflux of K+ ria smooth muscle K+ channels produces a local incr ease in [K+](o) which impairs repolarization to added K+. Thus, studies inv olving 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+.