Comparison of responses to aminoguanidine and N omega-nitro-L-arginine methyl ester in the rat aorta.
1. We have compared the effect of aminoguanidine with that of N omega-nitro-L-arginine methyl ester on isolated thoracic aortic rings obtained either from endotoxin (lipopolysaccharide, 10 mg/kg, i.v. for 3 h) or vehicle (saline) treated rats. 2. Administration of endotoxin for 3 h resulted in a hypotension and a significant reduction of pressor responses to norepinephrine (1 micrograms/kg, i.v.) in the anaesthetized rat. 3. In intact rings obtained from vehicle treated rats, aminoguanidine (0.3 and 1 mmol/L) had no significant effect on acetylcholine-induced relaxation (10(-9)-10(-5) mol/L), whereas N omega-nitro-L-arginine methyl ester (0.3 mmol/L and 1 mmol/L) abolished that response, suggesting that aminoguanidine does not inhibit the activity of constitutive nitric oxide synthase. 4. Relaxation induced by L-arginine (10(-6)-10(-2) mol/L) was competitively inhibited by both aminoguanidine (0.3 mmol/L) and N omega-nitro-L-arginine methyl ester (0.3 mmol/L) in endothelium-denuded aortic rings obtained from endotoxin treated rats. 5. Three hours of endotoxaemia was associated with an impairment of contraction to norepinephrine (10(-9)-10(-6) mol/L) in the endothelium-denuded aorta ex vivo. This hyporeactivity to norepinephrine was partially restored by treatment of the vessels either with aminoguanidine (0.3 mmol/L) or with N omega-nitro-L-arginine methyl ester (0.3 mmol/L) in vitro. 6. These results in isolated thoracic aortae of the rat reinforce that aminoguanidine is a selective inhibitor of the inducible nitric oxide synthase, whereas N omega-nitro-L-arginine methyl ester is a non-selective inhibitor of both the inducible and constitutive nitric oxide synthase.
Department of Pharmacology, National Defense Medical Center, Taipei, Taiwan, Republic of China.
M H
MH
Yen
S J
SJ
Chen
C C
CC
Wu
D000109:Acetylcholine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D001120:Arginine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006146:Guanidines / Q000494:pharmacology*; D066298:In Vitro Techniques; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D019331:NG-Nitroarginine Methyl Ester; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D009638:Norepinephrine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D000316:Adrenergic alpha-Agonists; D004791:Enzyme Inhibitors; D006146:Guanidines; D008070:Lipopolysaccharides; D001120:Arginine; D019001:Nitric Oxide Synthase; D000109:Acetylcholine; C004479:pimagedine; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine