Evidence against serotonin-induced endothelium-dependent relaxation in bovine coronary artery.

Bovine coronary artery rings were mounted in tissue baths for the measurement of isometric contraction in order to test for serotonin-induced endothelium-dependent relaxation. A23187 caused a concentration-dependent relaxation in precontracted artery rings when the endothelium was intact, but not when it was removed. Endothelium removal had no effect on serotonin concentration contractile response curves (CRC) in normal Krebs' solution, but enhanced the response to serotonin in artery rings precontracted with 25 mM K+ Krebs' solution. In endothelium-intact, precontracted artery rings, ketanserin shifted the serotonin CRC to the right, but did not convert the contraction to relaxation. 5-Carboxamidotryptamine caused a weak contraction that was blocked by ketanserin, but not converted to relaxation. Inactivation of monoamine oxidase enhanced the contractile response to serotonin in precontracted artery rings in a manner identical to that caused by endothelium removal. Inactivation of monoamine oxidase had no effect in endothelium-denuded artery rings. De-endothelialized rabbit aorta strips pretreated with phenoxybenzamine were placed in close apposition to endothelium-intact coronary artery strips. Superoxide dismutase, acetylcholine and A23187 caused the precontracted rabbit aorta strip to relax, whereas serotonin had no effect. These results support the conclusion that the endothelium of the bovine coronary artery releases a relaxing factor both spontaneously and in response to acetylcholine and A23187. Serotonin appears to be incapable of releasing endothelium-derived relaxing factor or causing an endothelium-dependent relaxation. However, bovine coronary artery endothelium appears to be able to take up and metabolize serotonin.