Spasmolytic effect of cromakalim in dog coronary artery in vitro.
Isometric force development was measured in isolated ring segments of dog left anterior descending coronary artery to K+ (10-70 mM), U-46619 (0.3-30 nM), endothelin-1 (0.1-30 nM), 5-HT (0.1-30 microM) and angiotensin-II (0.1-30 nM). Compared with the maximum tissue response to a K+ depolarizing solution (100%) there was a marked variation in the maximum response to each spasmogen: K+ (111%), U-46619 (85%), endothelin-1 (48%), 5-HT (49%) and angiotensin-II (15%). In arteries pretreated with cromakalim (0.3 - 10 microM) the maximum response to all constrictor agents (with the exception of K+) was reduced but the potency was unaffected. Maximum responses to angiotensin-II and 5-HT were affected at concentrations approximately threefold lower than those to endothelin-1 and U-46619. Removal of the endothelium increased the maximum response caused by 5-HT and reduced the potency of cromakalim in inhibiting this contraction. Glyceryl trinitrate and sodium nitroprusside were 100-1000 times more potent than cromakalim although they produced qualitatively similar effects. Cromakalim is an effective spasmolytic against a number of vasoconstrictors in the dog coronary artery. No marked spasmogen selectivity could be identified for cromakalim that was not shown by glyceryl trinitrate or sodium nitroprusside.
McPherson
G A
GA
Baker Medical Research Institute, Prahran, Victoria, Australia.
Keily
S G
SG
Angus
J A
JA
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology*; D003331:Coronary Vessels / Q000187:drug effects*; D019806:Cromakalim; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004730:Endothelium, Vascular / Q000502:physiology; D066298:In Vitro Techniques; D009126:Muscle Relaxation / Q000187:drug effects; D005996:Nitroglycerin / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D010276:Parasympatholytics / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology*; D012701:Serotonin / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology*
D001578:Benzopyrans; D010276:Parasympatholytics; D015221:Potassium Channels; D011450:Prostaglandin Endoperoxides, Synthetic; D011758:Pyrroles; D014665:Vasodilator Agents; D019806:Cromakalim; D009599:Nitroprusside; D012701:Serotonin; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D005996:Nitroglycerin