title: Increased endothelium-derived NO in hypertensive pulmonary circulation of chronically hypoxic rats.
abstract: The hypothesis that the endothelium-derived relaxing factor/nitric oxide (EDNO) activity is elevated in chronic hypoxic pulmonary hypertension (CH-PHT) was tested using isolated Krebs-albumin-perfused rat lungs. Concentration of the EDNO decomposition products (NOx) in the lungs' effluent was measured by a modified chemiluminescence assay. The functional significance of basal EDNO production was studied by measuring the vasoconstrictor response to an EDNO synthesis inhibitor, N omega-nitro-L-arginine methyl ester (L-NAME). Reactivity to the endothelium-dependent vasodilator substance P and to exogenous NO was also studied. More NOx was found in effluent from CH-PHT (22.3 +/- 9.8 nM) than control (0.4 +/- 3.9 nM) lungs. The L-NAME-induced vasoconstriction was greater in CH-PHT than in control rats. The sensitivity, but not the maximal vasodilation, to exogenous NO was elevated in CH-PHT. The substance P-induced vasodilation was potentiated in CH-PHT compared with control rats and blocked by L-NAME in both groups. We conclude that basal and agonist-stimulated pulmonary EDNO activity is enhanced in this model of CH-PHT. The EDNO synthesis may play a counterregulatory role in CH-PHT.
authors.affiliation: Department of Medicine, Veterans Affairs Medical Center, Minneapolis, Minnesota 55417.
authors.forename: T C
authors.initials: TC
authors.lastname: Isaacson
authors.forename: V
authors.initials: V
authors.lastname: Hampl
authors.forename: E K
authors.initials: EK
authors.lastname: Weir
authors.forename: D P
authors.initials: DP
authors.lastname: Nelson
authors.forename: S L
authors.initials: SL
authors.lastname: Archer
mesh_terms: D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002908:Chronic Disease; D006973:Hypertension / Q000150:complications / Q000503:physiopathology*; D000860:Hypoxia / Q000097:blood* / Q000150:complications / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000097:blood*; D011652:Pulmonary Circulation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013373:Substance P / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: D009569:Nitric Oxide; D013373:Substance P; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester