Does histamine influence vasodilation caused by prolonged arterial occlusion or heavy exercise?

Vasodilation induced by prolonged arterial occlusion or fatiguing exercise is thought by some to be due, in part, to histamine. To test this hypothesis, we studied isolated canine gracilis muscles perfused at low, constant flow. Diphenhydramine and cimetidine, H1 and H2 receptor antagonists, respectively, were used in combination. Vasodilation induced by a supramaximal dose of histamine was abolished but vasodilation after occlusions thought capable of inducing ischemic injury was unchanged in magnitude or time course. Vasodilation during moderate or heavy exercise at constant flow was also unaffected. We conclude that reactive hyperemia and exercise vasodilation in skeletal muscle do not depend even in part on histamine.