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.