Specific but differential antagonism by glibenclamide of the vasodepressor effects of cromakalim and nicorandil in spinally-anaesthetized dogs.
1. Whether the vasodepressor effects of cromakalim and nicorandil, potassium channel openers, were differentially antagonized by glibenclamide, a supposed specific antagonist of potassium channel openers, was investigated in spinally-anaesthetized dogs in which arterial pressure was maintained elevated by i.v. infusion of noradrenaline. 2. Cumulative administration of cromakalim (3-100 micrograms kg-1, i.v.), nicorandil (30-1000 micrograms kg-1, i.v.), diltiazem (3-300 micrograms kg-1, i.v.) and nitroglycerin (0.3-100 micrograms kg-1, i.v.) caused dose-dependent decreases in mean arterial pressure. In dogs which received glibenclamide (3 mg kg-1, i.v.), the dose-vasodepressor response curves for cromakalim and nicorandil were located on the right in parallel to the respective curves determined in control dogs, but those for diltiazem and nitroglycerin were not different. ED50% values increased about 6.7 fold for cromakalim and 2.2 fold for nicorandil. 3. The depression of LV dP/dtmax produced by a high dose of cromakalim (100 micrograms kg-1, i.v.) was abolished by glibenclamide and that produced by nicorandil was not only antagonized but converted to an increase. 4. These results suggest that the vasodepressor action of cromakalim is due predominantly to potassium channel opening, but that of nicorandil involves not only potassium channel opening but its action as a nitrate.
Yamada
H
H
Department of Pharmacology, Tohoku University School of Medicine, Sendai, Japan.
Yoneyama
F
F
Satoh
K
K
Taira
N
N
D000775:Anesthesia, Spinal; D000818:Animals; D001578:Benzopyrans / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D019806:Cromakalim; D004110:Diltiazem / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D005905:Glyburide / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D020108:Nicorandil; D005996:Nitroglycerin / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects*; D011758:Pyrroles / Q000037:antagonists & inhibitors* / Q000494:pharmacology
D001578:Benzopyrans; D002121:Calcium Channel Blockers; D015221:Potassium Channels; D011758:Pyrroles; D019806:Cromakalim; D009536:Niacinamide; D020108:Nicorandil; D004110:Diltiazem; D005996:Nitroglycerin; D005905:Glyburide; D009638:Norepinephrine