Potassium- and acetylcholine-induced vasorelaxation in mice lacking endothelial nitric oxide synthase

1 The contribution of an endothelium-derived hyperpolarizing factor (EDHF) was investigated in saphenous and mesenteric arteries from endothelial nitric oxide synthase (eNOS)(-/-) and (+/+) mice. 2 Acetylcholine-induced endothelium-dependent relaxation of saphenous arteries of eNOS(-/-) was resistant to N-omega-nitro-L-arginine (L-NNA) and indomethacin, as well as the guanylyl cyclase inhibitor. 1H-(1,2,4)oxadiazolo(4,3-a) quinoxalin-1-one(ODQ). 3 Potassium (K+) induced a dose-dependent vasorelaxation which was endothelium-independent and unaffected by either L-NNA or indomethacin in both saphenous and mesenteric arteries from eNOS(-/-) or (+/+) mice. 4 Thirty mu M barium (Ba2+) and 10 mu M ouabain partially blocked potassium-induced, but had no effect on acetylcholine-induced vasorelaxation in saphenous arteries. 5 Acetylcholine-induced relaxation was blocked by a combination of charybdotoxin (ChTX) and apamin which had no effect on K+-induced relaxation. however, iberiotoxin (IbTX) was ineffective against either acetylcholine- or K+-induced relaxation. 6 Thirty mu M Ba2+ partially blocked both K+- and acetylcholine-induced relaxation of mesenteric arteries, and K+. but not acetylcholine-induced relaxation was totally blocked by the combination of Ba2+ and ouabain. 7 These data indicate that acetylcholine-induced relaxation cannot be mimicked by elevating extracellular K+ in saphenous arteries from either eNOS(-/-) or (+/+) mice, but K+ may contribute to EDHF-mediated relaxation of mesenteric arteries.