Endothelium-derived nitric oxide regulates systemic and pulmonary vascular resistance during acute hypoxi 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 dat 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 NG-monomethyl-image-arginine (image-NMMA), nitric oxide synthase inhibitor, were studied in healthy volunteers under normoxic and hypoxic conditions. Swan-Ganz catheter and radial artery cannul 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 image-NMM (300 mg intravenously) was studied during normoxi in six subjects. Hypoxi was induced in eight subjects who inspired mixture of nitrogen and oxygen through gas blender adjusted to reduce the partial pressure of oxygen from (mean ± SE) 98 ± 4 to 48 ± 1 mm Hg. Results. During normoxia, image-NMM 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 ≤ 0.01 for each). Peak effects occurred within 10 min of image-NMM administration. Acute hypoxi alone decreased systemic vascular resistance from 1,209 ± 78 to 992 ± 58 dynes·s·cm−5 (p ≤ 0.05) and increased pulmonary vascular resistance from 92 ± 11 to 136 ± 4 dynes·s·cm−5 (p ≤ 0.01). While hypoxic conditions were maintained, infusion of image-NMM increased systemic vascular resistance (to 1,496 ± 97 dynes·s·cm−5, p ≤ 0.01) and increased pulmonary vascular resistance further (to 217 ± 25 dynes·s·cm−5, p ≤ 0.01). Conclusions. Endothelium-derived nitric oxide contributes to systemic vasodilation and serves as counterregulatory mechanism to attenuate pulmonary vasoconstriction during acute hypoxi in healthy human subjects.