We have determined the role of endogenous nitric oxide (NO) in regulation of vasomotor tone in ovine intrapulmonary and mesenteric vessels with resting tension and elevated vasomotor tone. Third generation intrapulmonary vessel rings and mesenteric vessel rings, 2-3 mm in diameter, were isolated from 20 sheep. NO production in the vessels was assessed by the change in tension induced by NG-nitro-L-arginine methyl ester (L-NAME), a competitive inhibitor of NO synthase. In vessels under resting tension, 10(-4) to 10(-3) M L-NAME induced a significant increase in tension only in veins but not in arteries. When tone was elevated with phenylephrine or U 46,619, a thromboxane A2 analogue, there was now a significant increase in tension in arteries with 10(-4) M L-NAME and in veins with 10(-5) M L-NAME. The increase in tension induced by L-NAME in veins was greater than that in arteries and greater when tone was elevated than under resting tension. Responses of pulmonary and mesenteric vessels were similar. Our data suggest that NO may play a role in regulating venous tone under baseline conditions and that the role of NO in regulation of vasomotor tone becomes more significant in the presence of nonspecific elevation of vasomotor tone in both arteries and veins. We speculate that endogenous NO production may be one mechanism by which pulmonary and systemic vessels counter the effects of vasoconstrictive agents.