N omega-nitro-L-arginine attenuates endothelium-dependent pulmonary vasodilation in lambs.
To investigate the role of endothelium-derived relaxing factor (EDRF) in the regulation of resting pulmonary vascular tone and endothelium-dependent pulmonary vasodilation, we studied the hemodynamic effects of N omega-nitro-L-arginine (a new stereospecific EDRF inhibitor) in 10 spontaneously breathing lambs and then compared the hemodynamic responses to five vasodilators during pulmonary hypertension induced by the infusion of U-46619 (a thromboxane A2 mimetic) or N omega-nitro-L-arginine. N omega-nitro-L-arginine caused a significant dose-dependent increase in pulmonary arterial pressure. Pretreatment with L-arginine blocked this increase, but pretreatment with D-arginine did not, suggesting that N omega-nitro-L-arginine is a competitive inhibitor of L-arginine for EDRF production. During U-46619 infusions, acetylcholine, ATP-MgCl2, isoproterenol, sodium nitroprusside, and 8-bromoguanosine 3',5'-cyclic monophosphate (8-bromo-cGMP) decreased pulmonary arterial pressure. During N omega-nitro-L-arginine infusions, the decrease in pulmonary arterial pressure caused by acetylcholine and ATP-MgCl2 (endothelium-dependent vasodilators) was significantly attenuated, but the decrease caused by isoproterenol, sodium nitroprusside, and 8-bromo-cGMP (endothelium-independent vasodilators) was unchanged. This study supports the hypothesis that EDRF in part mediates resting pulmonary vascular tone and endothelium-dependent pulmonary vasodilation. N omega-nitro-L-arginine is useful for studying EDRF inhibition in intact animals.
Fineman
J R
JR
Department of Pediatrics, University of California, San Francisco 94143.
Heymann
M A
MA
Soifer
S J
SJ
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000109:Acetylcholine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D001667:Binding, Competitive; D001794:Blood Pressure / Q000187:drug effects; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000502:physiology*; D006439:Hemodynamics / Q000187:drug effects; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000503:physiopathology; D007545:Isoproterenol / Q000494:pharmacology; D008168:Lung / Q000098:blood supply*; D009569:Nitric Oxide / Q000502:physiology*; D019335:Nitroarginine; D009599:Nitroprusside / Q000494:pharmacology; D011450:Prostaglandin Endoperoxides, Synthetic; D011651:Pulmonary Artery / Q000503:physiopathology; D012756:Sheep; D014664:Vasodilation / Q000187:drug effects*
D011450:Prostaglandin Endoperoxides, Synthetic; D009599:Nitroprusside; D019335:Nitroarginine; C016276:8-bromocyclic GMP; D009569:Nitric Oxide; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000255:Adenosine Triphosphate; D001120:Arginine; D006152:Cyclic GMP; D007545:Isoproterenol; D000109:Acetylcholine