Inhibition of nitric oxide synthase specifically enhances adrenergic vasoconstriction in rabbits.
1. The effect of inhibition of nitric oxide biosynthesis using N-nitro-L-arginine (NOLA) was examined in conscious rabbits and rabbit isolated aortae. 2. In autonomically blocked conscious rabbits intravenous infusion of NOLA (15 mg/kg) significantly increased arterial pressure and hindlimb vascular resistance but did not affect heart rate. Depressor and hindlimb vasodilator responses to acetylcholine (3-12 micrograms/kg per min) were significantly attenuated in the presence of NOLA. In contrast, NOLA significantly enhanced responses to intravenous infusion of glyceryl trinitrate (10-40 micrograms/kg per min) in vivo. 3. Infusion of noradrenaline (1-4 micrograms/kg per min) or the release of neuronal noradrenaline in response to the infusion of tyramine (80-320 micrograms/kg per min) increased arterial pressure and hindlimb vascular resistance in autonomically blocked conscious rabbits. After the administration of NOLA, the vasoconstrictor responses to both noradrenaline and tyramine were significantly enhanced. 4. In isolated rabbit aortae, NOLA (10 mumol/L) significantly impaired relaxant responses to acetylcholine but did not affect responses to glyceryl trinitrate. NOLA enhanced contractile responses to the adrenoceptor agonists noradrenaline and phenylephrine but did not affect the contractile responses to the thromboxane-mimetic U46619. 5. These data indicate that in autonomically blocked conscious rabbits, NOLA causes systemic vasoconstriction, impairs dilator responses to acetylcholine and enhances dilator responses to glyceryl trinitrate. In addition, NOLA enhances constrictor responses to both exogenous and neuronally-released noradrenaline. These results suggest that nitric oxide is important in the regulation of normal vascular tone and in the modulation of vascular responses to vasodilator and vasoconstrictor agents.
Du
Z Y
ZY
Department of Pharmacology, University of Melbourne, Parkville, Victoria, Australia.
Dusting
G J
GJ
Woodman
O L
OL
D000109:Acetylcholine / Q000037:antagonists & inhibitors; D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects*; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004357:Drug Synergism; D004837:Epinephrine / Q000502:physiology*; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D019001:Nitric Oxide Synthase; D019335:Nitroarginine; D005996:Nitroglycerin / Q000494:pharmacology; D011817:Rabbits; D014439:Tyramine / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology*
D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D019335:Nitroarginine; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D005996:Nitroglycerin; D000109:Acetylcholine; D014439:Tyramine; D004837:Epinephrine