Acute and chronic inhibition of nitric oxide synthase in conscious rabbits: role of nitric oxide in the control of vascular tone.
Acute and chronic effects of Nw-nitro-L-arginine (L-NNA), an inhibitor of nitric oxide synthase, were examined on the hindquarter hemodynamics of conscious rabbits. After pharmacological autonomic reflex blockade on four experimental days (days 0, 1, 2, and 7), responses to aortic occlusion (balloon cuff, 5-80 s inflation), intra-aortic infusion of acetylcholine, adenosine, and sodium nitroprusside (SNP) were measured before and after vehicle (day 0) or L-NNA (16 mg/kg/h i.v., days 1, 2, and 7). On day 1, L-NNA raised the mean arterial pressure (MAP), and lowered the heart rate (HR) and hindquarter vascular conductance (HVC = abdominal aortic Doppler blood flow/MAP). On days 2 and 7, L-NNA only slowly raised the MAP. The dilator response to acetylcholine was inhibited by L-NNA on day 1 and before and after L-NNA on days 2 and 7. The responses to aortic occlusion, adenosine, or SNP infusion were unaffected by L-NNA treatment on any day. Thus, if nitric oxide synthase inhibition by L-NNA abolishes NO release, then (i) reactive hyperaemia is independent of NO, (ii) basal NO release normalises the arterial pressure in the short term but other factors become important in the long term, and (iii) the blockade by L-NNA of receptor-stimulated NO release by acetylcholine is only very slowly reversible.
Ward
J E
JE
Baker Medical Research Institute, Prahran, Victoria, Australia.
Angus
J A
JA
D000109:Acetylcholine / Q000494:pharmacology; D000241:Adenosine / Q000494:pharmacology; D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D005730:Ganglionic Blockers / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006614:Hindlimb / Q000098:blood supply; D006940:Hyperemia / Q000503:physiopathology; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D009129:Muscle Tonus / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase; D019335:Nitroarginine; D009599:Nitroprusside / Q000494:pharmacology; D011817:Rabbits; D012039:Regional Blood Flow / Q000187:drug effects
D005730:Ganglionic Blockers; D009599:Nitroprusside; D019335:Nitroarginine; D009569:Nitric Oxide; D008464:Mecamylamine; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D000241:Adenosine; D000109:Acetylcholine