Role of gap junctions in the responses to EDHF in rat and guinea-pig smallarteries

1 In guinea-pig internal carotid arteries with an intact endothelium, acety lcholine (10 mu M) and levcromakalim (10 mu M) each hyperpolarized the smoo th muscle whereas a 5 mM elevation of extracellular K+ was without effect. 2 Incubation of the carotid artery with the gap junction inhibitors carbeno xolone (100 mu M) or gap 27 (500 mu M) essentially abolished the hyperpolar ization to acetylcholine but it was without effect on that to levcromakalim . Carbenoxolone had no effect on the acetylcholine-induced endothelial cell hyperpolarization but inhibited the smooth muscle hyperpolarization induce d by the endothelial cell K+ channel opener, 1-ethyl-2-benzimidazolinone (6 00 mu M). 3 In rat hepatic and mesenteric arteries with endothelium, carbenoxolone (1 00 or 500 mu M) depolarized the smooth muscle but did not modify hyperpolar izations induced by KCl or levcromakalim. In the mesenteric (but not the he patic) artery, the acetylcholine-induced hyperpolarization was inhibited by carbenoxolone. 4 Phenylephrine (1 mu M) depolarized the smooth muscle cells of intact hepa tic and mesenteric arteries. an effect enhanced by carbenoxolone. Gap 27 di d not have a depolarizing action. In the presence of phenylephrine, acetylc holine-induced hyperpolarization of both hepatic and mesenteric artery myoc ytes was partially inhibited by each of the gap junction inhibitors. 5 Collectively, the data suggest that gap junctions play some role in the E DI-IF (endothelium-derived hyperpolarizing factor) response in rat hepatic and mesenteric arteries. However, in the guinea-pig internal carotid artery , electrotonic propagation of endothelial cell hyperpolarizations via gap j unctions may be the sole mechanism underlying the response previously attri buted to EDHF.