Endogenous endothelium-derived relaxing factor opposes hypoxic pulmonary vasoconstriction and supports blood flow to hypoxic alveoli in anesthetized rabbits.
Agents that inhibit nitric oxide synthesis augment hypoxic pulmonary vasoconstriction. In an animal model of unilateral alveolar hypoxia, we investigated the hypothesis that endogenous endothelium-derived relaxing factor/nitric oxide opposes hypoxic pulmonary vasoconstriction and supports blood flow to hypoxic alveoli, resulting in a reduction in arterial oxygen tension (PO2). In pentobarbital-anesthetized rabbits, unilateral alveolar hypoxia was produced by ventilation of one lung with 100% oxygen and the other with 100% nitrogen (O2/N2). NG-Nitro-L-arginine methyl ester (0.03 followed by 1.0 mg/kg i.v.) resulted in dose-dependent decreases in the percent of pulmonary blood flow to the N2-ventilated lung and increases in arterial PO2. L-Arginine (1 mg.kg-1.min-1 i.v.) prevented the NG-nitro-L-arginine methyl ester-induced redistribution of blood flow away from hypoxic alveoli and improvement in arterial PO2. Indomethacin (5 mg/kg i.v.) administered during O2/N2 ventilation resulted in a reduction in the percentage of total blood flow to the hypoxic lung and an increase in arterial PO2. However, NG-nitro-L-arginine methyl ester administered in the presence of indomethacin caused additional diversion of blood flow away from the hypoxic lung. The magnitude of the changes suggests that the endothelium-derived relaxing factor/nitric oxide system has the capacity to make a greater contribution than products of cyclooxygenase-mediated arachidonic acid metabolism in supporting blood flow to hypoxic alveoli in the rabbit.
Sprague
R S
RS
William Harvey Research Institute, St. Bartholomew's Hospital Medical College, London, United Kingdom.
Thiemermann
C
C
Vane
J R
JR
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D000860:Hypoxia / Q000503:physiopathology*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000494:pharmacology / Q000502:physiology*; D011650:Pulmonary Alveoli / Q000098:blood supply*; D011652:Pulmonary Circulation; D011817:Rabbits; D012039:Regional Blood Flow / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects
D009569:Nitric Oxide; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin