Flutamide induces relaxation in large and small blood vessels.

HYPOTHESIS Flutamide, a testosterone receptor antagonist, produces various beneficial effects in male rats following hemorrhagic shock, possibly as a result of a direct vasodilating effect on large and small vessels in the rat. DESIGN, INTERVENTIONS, AND MAIN OUTCOME MEASURES The aorta and the small intestine were isolated from normal male and female Sprague-Dawley rats. Isolated aortic rings were placed in the organ bath and constricted by 2 x 10(-7)M norepinephrine bitartrate (Sigma, St Louis, Mo). Flutamide-induced and testosterone-induced vascular relaxation dose-response curves were then determined. The dose-response curves of flutamide were also determined in the small blood vessels of the isolated small intestine under conditions of constant flow following preconstriction induced by 5 x 10(-6 )M norepinephrine bitartrate. The effects of prior incubation with testosterone (8 x 10(-5)M) and sex differences on flutamide-induced vascular relaxation were also examined in aortic rings and in the small intestine. Moreover, flutamide-induced relaxation in endothelium-denuded aortic rings and in aortic rings from animals subjected to trauma and hemorrhagic shock was examined. RESULTS Flutamide induced significant relaxation in aortic rings and small intestinal blood vessels in healthy males. The flutamide-induced relaxation in vessels from normal males was partially attenuated by prior incubation with the male sex steroid testosterone, and was significantly lower in females. Flutamide-induced vascular relaxation in the aorta was partially attenuated by endothelium removal, but it was not significantly affected by trauma and hemorrhagic shock in male rats. CONCLUSIONS Flutamide has a direct vasodilating effect on large and small vessels in rats, which involves sex-dependent mechanisms. Thus, the beneficial effects of flutamide on cardiovascular responses in males following trauma and hemorrhagic shock may be due to the direct vascular relaxation induced by this agent.