L-NAME enhances pulmonary vasoconstriction without inhibiting EDRF-dependent vasodilation.
The purpose of the present study was to determine the influence of NG-nitro-L-arginine methyl ester (L-NAME) on pulmonary vascular responses to endothelium-dependent relaxing factor- (EDRF) dependent and EDRF-independent substances in the pulmonary vascular bed of the anesthetized cat. Because pulmonary blood flow and left atrial pressure were kept constant, changes in lobar arterial pressure directly reflect changes in pulmonary vascular resistance. When pulmonary vasomotor tone was actively increased by intralobar infusion of U-46619, intralobar bolus injections of acetylcholine, bradykinin, serotonin, and 5-carboxyamidotryptamine (a serotonin1A receptor agonist) decreased lobar arterial pressure in a dose-related manner. The pulmonary vasodilator response to serotonin, but not to 5-carboxyamidotryptamine, acetylcholine, and bradykinin, was significantly decreased by L-NAME (100 mg/kg i.v.). Administration of ritanserin (0.5 mg/kg i.v.), but not L-arginine (1 g/kg i.v. with 60 mg.kg-1 x min-1 i.v. infusion), reversed the inhibitory effects of L-NAME on the pulmonary vasodilator response to serotonin and abolished the enhanced pulmonary vasoconstrictor response to (+-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminoproprane hydrochloride (a serotonin2 receptor agonist) after L-NAME administration. In conclusion, the present experiments suggest that L-NAME inhibits the pulmonary vasodilator response to serotonin by increasing the sensitivity of serotonin2 receptor-mediated vasoconstriction and not by inhibiting EDRF formation. Because the pulmonary vasodilator responses to bolus administration of acetylcholine and bradykinin were not inhibited by L-NAME, these data suggest that L-NAME does not appear to be an adequate probe to study the role of endogenous EDRF in the adult feline pulmonary vascular bed in vivo.
Lippton
H L
HL
Department of Internal Medicine, Louisiana State University Medical School, New Orleans.
Hao
Q
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Hyman
A
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D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000662:Amphetamines / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001645:Biguanides / Q000494:pharmacology; D002415:Cats; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011652:Pulmonary Circulation / Q000187:drug effects*; D012701:Serotonin / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*
D000662:Amphetamines; D001645:Biguanides; D007004:Hypoglycemic Agents; D011450:Prostaglandin Endoperoxides, Synthetic; D017366:Serotonin Receptor Agonists; D014662:Vasoconstrictor Agents; D009569:Nitric Oxide; D012701:Serotonin; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D001120:Arginine; D007545:Isoproterenol; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine; D019331:NG-Nitroarginine Methyl Ester; C008846:phenyl biguanide