N omega-nitro-L-arginine and pulmonary vascular pressure-flow relationship in conscious dogs.
We investigated the effects of an inhibitor of nitric oxide (NO) synthesis, N omega-nitro-L-arginine (L-NNA), on the pulmonary vascular pressure-flow relationship in chronically instrumented conscious dogs. The L-arginine analogue L-NNA (20 mg/min for 60 min iv) had no effect on the baseline pressure-flow relationship. This result indicates that tonic release of endothelium-derived relaxing factor (EDRF), which is thought to be NO or a labile NO-generating molecule, is not responsible for low resting pulmonary vasomotor tone in conscious dogs. In contrast, L-NNA caused a leftward shift in the dose-response relationship to the thromboxane mimetic U-46619, indicating that the endogenous release of EDRF modulates the pulmonary vascular response to this vasoconstrictor. Finally, after preconstriction with U-46619, L-NNA abolished the pulmonary vasodilator response to bradykinin (1-10 micrograms.kg-1.min-1) but had no effect on the pulmonary vasodilator response to sodium nitroprusside (1-10 micrograms.kg-1.min-1). Thus EDRF does not appear to tonically regulate the baseline pulmonary vascular pressure-flow relationship in conscious dogs. However, EDRF does act to attenuate the magnitude of U-46619-induced pulmonary vasoconstriction. Moreover, the pulmonary vasodilator response to bradykinin is entirely mediated by EDRF in conscious dogs.
Nishiwaki
K
K
Department of Anesthesiology/Critical Care Medicine, Johns Hopkins Medical Institutions, Baltimore, Maryland 21205.
Nyhan
D P
DP
Rock
P
P
Desai
P M
PM
Peterson
W P
WP
Pribble
C G
CG
Murray
P A
PA
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D001920:Bradykinin / Q000494:pharmacology; D004285:Dogs; D008297:Male; D019335:Nitroarginine; D009599:Nitroprusside / Q000494:pharmacology; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011652:Pulmonary Circulation / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D011450:Prostaglandin Endoperoxides, Synthetic; D014662:Vasoconstrictor Agents; D009599:Nitroprusside; D019335:Nitroarginine; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D001120:Arginine; D001920:Bradykinin