The effect of the nitric oxide synthase inhibitor N-gamma-nitro-L-argine methyl ester on hypoxic pulmonary vasoconstriction.
We studied the role of nitric oxide in the regulation of pulmonary arterial tone and hypoxic pulmonary vasoconstriction. Rat pulmonary arteries (n=65, diameter=440+/-12 microm) were loaded to 17.5 mm Hg in a wire myograph and incubated with the nitric oxide synthase inhibitor N-gamma-nitro-L-argine methyl ester (L-NAME; 1, 10 or 100 microM) or distilled water (50 microl) prior to preconstriction with either 100 microM prostaglandin F(2 alpha) followed by acetylcholine (0.1-100 microM) or 5 microM prostaglandin F(2 alpha) followed by hypoxia. Concentrations of L-NAME (10 and 100 microM) which attenuated acetylcholine dilatation, elevated basal tone from 0. 2+/-0.5% to 9.4+/-2.1% (P<0.01) and 18.3+/-3.2% (P<0.001), respectively, potentiated contraction to 5 microM prostaglandin F(2 alpha) from 35.9+/-3.1% to 56.2+/-6.8% (P<0.05) and 66.4+/-5.8% (P<0.001), respectively, but had no significant effect on hypoxic pulmonary vasoconstriction. This suggests basal pulmonary nitric oxide release occurs, as well as in response to agonist-induced contraction, but not hypoxic pulmonary vasoconstriction.
Section of Respiratory Medicine, Academic Department of Medicine, The University of Hull, Castle Hill Hospital, Cottingham, UK. r.d.jones@sheffield.ac.uk
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D000818:Animals; D015237:Dinoprost / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D000860:Hypoxia / Q000503:physiopathology*; D008297:Male; D009129:Muscle Tonus / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D052250:Nitric Oxide Synthase Type III; D011652:Pulmonary Circulation / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D014661:Vasoconstriction / Q000187:drug effects*
D004791:Enzyme Inhibitors; D015237:Dinoprost; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D019331:NG-Nitroarginine Methyl Ester