title: Potassium- and acetylcholine-induced vasorelaxation in mice lacking endothelial nitric oxide synthase.
abstract: 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 microM barium (Ba(2+)) and 10 microM 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 microM Ba(2+) 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 Ba(2+) 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.
authors.affiliation: Department of Pharmacology & Therapeutics & The Smooth Muscle Research Group, Faculty of Medicine, University of Calgary, Calgary, Alberta, T2N 4N1 Canada.
authors.forename: H
authors.initials: H
authors.lastname: Ding
authors.forename: P
authors.initials: P
authors.lastname: Kubes
authors.forename: C
authors.initials: C
authors.lastname: Triggle
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D001030:Apamin / Q000494:pharmacology; D001158:Arteries / Q000187:drug effects; D001464:Barium / Q000494:pharmacology; D001685:Biological Factors / Q000494:pharmacology; D018999:Charybdotoxin / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D008642:Mesenteric Veins / Q000187:drug effects; D051379:Mice; D018345:Mice, Knockout; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000172:deficiency* / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D019335:Nitroarginine / Q000494:pharmacology; D010042:Ouabain / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology*; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors; D000098854:Kcnj10 Channel
chemical_list: D001685:Biological Factors; D004791:Enzyme Inhibitors; D000098854:Kcnj10 Channel; D010455:Peptides; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; C067410:endothelium-dependent hyperpolarization factor; D018999:Charybdotoxin; D019335:Nitroarginine; D001030:Apamin; D001464:Barium; D010042:Ouabain; C064719:iberiotoxin; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; D000254:Sodium-Potassium-Exchanging ATPase; D000109:Acetylcholine; D011188:Potassium