Effects of K+ channel openers on relaxations to nitric oxide and endothelium-derived hyperpolarizing factor in rat mesenteric artery.
Relaxation of methoxamine-precontracted, endothelium-intact, rat mesenteric artery in the presence of NG-nitro-L-arginine methyl ester (L-NAME; 100 microM) and indomethacin (10 microM) is attributed to endothelium-derived hyperpolarizing factor (EDHF). The potency of carbachol in the presence (but not the absence) of L-NAME was reduced by levcromakalim and pinacidil, activators of ATP-sensitive K+ channels (KATP). EDHF-mediated relaxation to Ca2+ ionophore A23187 was unaffected by these compounds but was inhibited by verapamil at the level of the smooth muscle. Levcromakalim and pinacidil had the same effects at both reduced and standard levels of tone. Glibenclamide (10 microM), a KATP blocker, alone did not affect carbachol relaxations but abolished both relaxation to levcromakalim and pinacidil and their inhibitory action on EDHF released by carbachol. Levcromakalim inhibited the endothelium-dependent hyperpolarization of mesenteric arteries to carbachol but not to A23187. Thus, levcromakalim or pinacidil inhibit EDHF, but not nitric oxide, release by carbachol through an action on the endothelium.
White
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Department of Pharmacology, University of Cambridge, UK.
Hiley
C R
CR
D000818:Animals; D001685:Biological Factors / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000502:physiology; D000001:Calcimycin / Q000494:pharmacology; D019806:Cromakalim / Q000494:pharmacology; D004347:Drug Interactions; D004594:Electrophysiology; D004730:Endothelium, Vascular / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007476:Ionophores / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials; D008638:Mesenteric Arteries / Q000187:drug effects / Q000378:metabolism; D009126:Muscle Relaxation / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009569:Nitric Oxide / Q000502:physiology; D015221:Potassium Channels / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar
D001685:Biological Factors; D004791:Enzyme Inhibitors; D007476:Ionophores; D015221:Potassium Channels; C067410:endothelium-dependent hyperpolarization factor; D019806:Cromakalim; D009569:Nitric Oxide; D000001:Calcimycin; D019331:NG-Nitroarginine Methyl Ester