Spasmolytic effect of cromakalim in dog coronary artery in vitro

Summary 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 M) 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 M) 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 Comakalim that was not shown by glyceryl trinitrate or sodium nitroprusside. Send offprint requests to G. A. McPherson at the above address