Oxygen or low concentrations of nitric oxide reverse pulmonary vasoconstriction induced by nitric oxide synthesis inhibition in rabbits.
The objective of this study was to investigate the role of nitric oxide and oxygen in the regulation of pulmonary vascular resistance, especially by means of substitution with nitric oxide after inhibition of endogenous nitric oxide formation. In artificially ventilated open-chest rabbits pulmonary vascular resistance at normoxic ventilation (FIO2 = 21%) was 56 +/- 6 cmH2O ml-1 min-1 1000-1 (mRUL). N omega-nitro-L-arginine methyl ester (L-NAME, 30 mg kg-1), an inhibitor of NO synthase, increased pulmonary vascular resistance to 122 +/- 17 mRUL at normoxic ventilation. In response to L-NAME there was also an increase in mean arterial blood pressure. Exogenous nitric oxide (0.014-9 p.p.m. in the inhaled air) dose-dependently and reversibly counteracted the effect of L-NAME on pulmonary vascular resistance at normoxic ventilation, without affecting systemic blood pressure. In addition, the L-NAME-induced vasoconstriction was critically dependent on oxygen. Thus, during hypoxic ventilation (FIO2 = 10%) the pulmonary vascular resistance was increased approximately four-fold by the presence of L-NAME (30 mg kg-1), and increments in FIO2 (21-100%) dose-dependently and reversibly counteracted the effect of L-NAME on pulmonary vascular resistance. Taken together these findings demonstrate that inhalation of low doses of NO may act as a replacement when endogenous NO synthesis is inhibited, and that pulmonary vasoconstriction induced by NO synthesis inhibition is likely to be the result of interference with oxygen-dependent regulatory mechanisms. Endogenous NO co-operates with oxygen to evoke a vasodilator component of the pulmonary hypoxic pressor response, balancing a hitherto unknown constrictor mechanism.
Persson
M G
MG
Department of Physiology, Karolinska Institute, Stockholm, Sweden.
Kalzén
H
H
Gustafsson
L E
LE
D000280:Administration, Inhalation; D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000494:pharmacology*; D019001:Nitric Oxide Synthase; D009994:Osmolar Concentration; D010100:Oxygen / Q000494:pharmacology*; D011652:Pulmonary Circulation / Q000187:drug effects*; D011817:Rabbits; D014661:Vasoconstriction / Q000187:drug effects*
D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D010100:Oxygen; D019331:NG-Nitroarginine Methyl Ester