Endothelium-derived nitric oxide regulates systemic and pulmonary vascular resistance during acute hypoxia in humans

Objectives. This investigation sought to determine whether endothelium-derived nitric oxide contributes to hypoxia-induced systemic vasodilation and pulmonary vasoconstriction in humans. Background. Endothelium derived nitric oxide contributes to basal systemic and pulmonary vascular resistance. During hypoxia, systemic vasodilation and pulmonary vasoconstriction occur. There are some data indicating that endothelium-derived nitric oxide mediates changes in vascular resistance during hypoxia, but much of it is contradictory, and none has been derived from normal humans. Methods. The hemodynamic effects of N-G-monomethyl-L-arginine (L-NMMA), a nitric oxide synthase inhibitor, were studied in healthy volunteers under normoxic and hypoxic conditions. A Swan-Ganz catheter and radial artery cannula were inserted to measure right atrial, pulmonary artery, pulmonary capillary wedge and systemic blood pressures. Cardiac output was measured by thermodilution. Systemic vascular resistance and pulmonary vascular resistance were calculated. The pharmacokinetics of L-NMMA (300 mg intravenously) was studied during normoxia in six subjects. Hypoxia was induced in eight subjects who inspired a mixture of nitrogen and oxygen through a gas blender adjusted to reduce the partial pressure of oxygen from (mean +/- SE) 98 +/- 4 to 48 +/- 1 mm Hg. Results. During normoxia, L-NMMA increased systemic vascular resistance from 1,108 +/- 74 to 1,705 +/- 87 dynes . s . cm(-5) and increased pulmonary vascular resistance from 60 +/- 5 to 115 +/- 9 dynes . s . cm(-5) (p less than or equal to 0.01 for each). Peak effects occurred within 10 min of L-NMMA administration. Acute hypoxia alone de creased systemic vascular resistance from 1,209 +/- 78 to 992 +/- 58 dynes . s . cm(-5) (p less than or equal to 0.05) and increased pulmonary vascular resistance from 92 +/- 11 to 136 +/- 4 dynes . s . cm(-5) (p less than or equal to 0.01). While hypoxic conditions were maintained, infusion of L-NMMA in creased systemic vascular resistance (to 1,496 +/- 97 dynes . s . cm(-5), p less than or equal to 0.01) and increased pulmonary vascular resistance further (to 217 +/- 25 dynes . s . cm(-5), p less than or equal to 0.01). Conclusions. Endothelium derived nitric oxide contributes to systemic vasodilation and serves as a counterregulatory mechanism to attenuate pulmonary vasoconstriction during acute hypoxia in healthy human subjects.