ENDOTHELIUM-INDUCED RELAXATION BY ACETYLCHOLINE ASSOCIATED WITH LARGER RISES IN CYCLIC-GMP IN CORONARY ARTERIAL STRIPS

Abstract

The contractile response to acetylcholine (ACh) in bovine coronary arterial strips could be separated from the accompanying rises in cGMP in an opposite manner which suggested that this nucleotide may function as a relaxation, rather than a contraction promoting agent. It was also found recently by others that rings or strips of rabbit aorta and other arteries of various species relax in response to ACh if endothelial cells are still present. The influence of endothelium on the mechanical effects as well as on rises in cGMP levels produced by ACh was therefore studied in circular strips of bovine coronary arteries with and without endothelium. Endothelium-depleted strips, precontracted with 25 .mu.M serotonin were not further contracted by ACh which raised cGMP-levels to 3.5-fold the control value. Endothelium-preserved strips, however, were relaxed by ACh and showed significantly higher increases in cGMP up to 7-fold the control value. ACh-induced relaxation and rises in cGMP in endothelium-containing strips were significantly potentiated by a preferential inhibitor of cGMP-PDE (MB-22,948 [2-O-propoxyphenyl-8-azpurin-6-one]), and both effects were abolished by methylene blue. Apparently, the relaxation promoting influence of endothelium is associated with an augmented rise in cGMP.