Nitric oxide generation and hypoxic vasoconstriction in buffer-perfused rabbit lungs.
Nitric oxide generation and hypoxic vasoconstriction in buffer-perfused rabbit lungs. J. Appl. Physiol. 78(4): 1509-1515, 1995.--We investigated the role of nitric oxide (NO) generation in hypoxic pulmonary vasoconstriction in buffer-perfused rabbit lungs. Exhaled NO was detected by chemiluminescence, and intravascular NO release was quantified as perfusate accumulation of nitrite, peroxynitrite, and nitrate (NOx). Under baseline conditions, exhaled NO was 45.3 +/- 4.1 parts per billion (1.8 +/- 0.2 nmol/min), and lung NOx release into the perfusate was 4.1 +/- 0.4 nmol/min. Alveolar hypoxia (alveolar PO2 of approximately 23 Torr) induced readily reproducible pressor responses preceded by a sharp drop in exhaled NO concentration. In contrast, perfusate NOx accumulation was not affected. Vasoconstrictor responses to U-46619 and angiotensin II were not accompanied by a decrease in NO exhalation. NG-monomethyl-L-arginine dose-dependently suppressed NO exhalation and amplified pressor responses to hypoxia > U-46619 and angiotensin II. In conclusion, portions of baseline NO generation originating from sites with ready access to the gaseous space sharply decrease in response to alveolar hypoxia, whereas the intravascular release of NO is unchanged. Such differential regulation of lung NO synthesis in response to hypoxia may suggest a complex role in the regulation or modulation of hypoxic pulmonary vasoconstriction.
Grimminger
F
F
Department of Internal Medicine, Justus-Liebig University, Giessen, Germany.
Spriestersbach
R
R
Weissmann
N
N
Walmrath
D
D
Seeger
W
W
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D000860:Hypoxia / Q000378:metabolism*; D066298:In Vitro Techniques; D008168:Lung / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis*; D010477:Perfusion; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011652:Pulmonary Circulation / Q000187:drug effects / Q000502:physiology*; D011817:Rabbits; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D019323:omega-N-Methylarginine
D011450:Prostaglandin Endoperoxides, Synthetic; D000804:Angiotensin II; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D001120:Arginine