NITRIC-OXIDE REGULATES BASAL SYSTEMIC AND PULMONARY VASCULAR-RESISTANCE IN HEALTHY HUMANS

Background The endothelium synthesizes and releases a relaxing factor with the physiochemical properties of nitric oxide (NO). However, the role of endothelium-derived NO in the basal regulation of systemic and pulmonary vascular resistance in humans is not known. Our primary obj ectives were to determine the effects of inhibiting NO synthesis on bl ood pressure and systemic vascular resistance and to establish the rol e of endothelium-derived NO in the regulation of normoxic pulmonary va scular tone. Methods and Results We studied the systemic and pulmonary hemodynamic effects of NO-monomethyl-L-arginine (L-NMMA, 0.03 to 1.0 mg . kg(-1) . min(-1) IV), an NO synthase inhibitor, in 11 healthy vol unteers, aged 33+/-2 years. An arterial cannula and a pulmonary artery catheter were placed in each subject to measure blood pressure, pulmo nary artery pressure, and pulmonary capillary wedge pressure. Cardiac output was determined by the Fick technique, and systemic and pulmonar y vascular resistances were calculated. Serum NO levels (free and prot ein bound) were measured by chemiluminescence in 5 subjects. Six of th e subjects also received phenylephrine (25 to 100 mu g/min IV) to comp are the cardiac hemodynamic effects of L-NMMA with those of a direct-a cting vasoconstrictor. L-NMMA caused dose-dependent increases in both blood pressure and systemic vascular resistance. At the highest dose o f L-NMMA, there was a 15.5+/-1.3% increase in mean blood pressure and a 63.4+/-8.2% increase in systemic vascular resistance (each P<.01). P ulmonary vascular resistance increased 39.8+/-9.4% (P<.01), whereas me an pulmonary artery pressure did not change. Administration of L-NMMA also reduced cardiac output by 27.8+/-2.9% and stroke volume by 15.4+/ -3.5% (each P<.01). Serum NO levels decreased 65+/-10% from basal valu es (P<.05), confirming inhibition of endogenous NO production. Phenyle phrine increased blood pressure to a level comparable to that observed with L-NMMA. The decline in stroke volume was greater with L-NMMA tha n with phenylephrine (P<.01). Conclusions This study demonstrates that basal release of endothelium-derived NO is directly involved in the d etermination of systemic vascular resistance and, therefore, blood pre ssure in healthy humans. In addition, NO regulates baser normoxic pulm onary vascular tone. The complex hemodynamic effects of NO are composi te properties of its actions on systemic and pulmonary vascular resist ance and cardiac function.