Abstract | OBJECTIVES: BACKGROUND: METHODS: The hemodynamic effects of NG-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 < or = 0.01 for each). Peak effects occurred within 10 min of L-NMMA administration. Acute hypoxia alone decreased systemic vascular resistance from 1,209 +/- 78 to 992 +/- 58 dynes-s-cm-5 (p < or = 0.05) and increased pulmonary vascular resistance from 92 +/- 11 to 136 +/- 4 dynes-s-cm-5 (p < or = 0.01). While hypoxic conditions were maintained, infusion of L-NMMA increased systemic vascular resistance (to 1,496 +/- 97 dynes-s-cm-5, p < or = 0.01) and increased pulmonary vascular resistance further (to 217 +/- 25 dynes-s-cm-5, p < or = 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.
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Authors | M L Blitzer, E Loh, M A Roddy, J S Stamler, M A Creager |
Journal | Journal of the American College of Cardiology
(J Am Coll Cardiol)
Vol. 28
Issue 3
Pg. 591-6
(Sep 1996)
ISSN: 0735-1097 [Print] United States |
PMID | 8772744
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- omega-N-Methylarginine
- Nitric Oxide
- Arginine
- Nitric Oxide Synthase
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Topics |
- Acute Disease
- Adult
- Arginine
(analogs & derivatives, pharmacokinetics, pharmacology)
- Blood Pressure
(drug effects)
- Female
- Hemodynamics
(drug effects)
- Humans
- Hypoxia
(physiopathology)
- Male
- Nitric Oxide
(physiology)
- Nitric Oxide Synthase
(antagonists & inhibitors)
- Pulmonary Circulation
(drug effects, physiology)
- Vascular Resistance
(drug effects, physiology)
- Vasoconstriction
(drug effects, physiology)
- Vasodilation
(drug effects, physiology)
- omega-N-Methylarginine
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