Combined therapy with inhaled nitric oxide and intravenous vasodilators during acute and chronic experimental pulmonary hypertension

Both inhaled nitric oxide (NO) and TV vasodilators decrease pulmonary hyper tension, but the effects of combination therapy are unknown. We studied the response to inhaled NO 100 ppm alone, IV vasodilator alone, and combined t herapy during acute (U46619-induced) and chronic (monacrotaline-induced) pu lmonary hypertension in the pentobarbital-anesthetized rat. Vasodilator dos es were 1.0, 3.2, 10, and 32 mu g kg(-1) min(-1) sodium nitroprusside (SNP) ; 50, 100, 150, 200, and 300 mu g kg(-1) min(-1) adenosine; or 25, 50, 150, 200, and 300 mu g kg(-1) min(-1) prostacyclin. in the absence of TV vasodi lator therapy, inhaled NO decreased mean pulmonary artery pressure without decreasing mean systemic arterial pressure. In both acute and chronic pulmo nary hypertension, the addition of inhaled NO to the largest dose of adenos ine or prostacyclin, but not of SNP, decreased pulmonary artery pressure. B ecause inhaled NO and SNP activate guanylyl cyclase and adenosine and prost acyclin activate adenylyl cyclase, the results suggest that adding inhaled NO to a vasodilator not dependent on gunnylyl cyclase may produce additiona l selective pulmonary vasodilation. Implications: in therapy of pulmonary h ypertension, inhaled nitric oxide should produce additional selective pulmo nary vasodilation when combined with a vasodilator whose mechanism of actio n is not dependent on cyclic guanosine 3'5'-monophosphate.