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Comparison of responses to aminoguanidine and N omega-nitro-L-arginine methyl ester in the rat aorta.

Abstract
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.
AuthorsM H Yen, S J Chen, C C Wu
JournalClinical and experimental pharmacology & physiology (Clin Exp Pharmacol Physiol) Vol. 22 Issue 9 Pg. 641-5 (Sep 1995) ISSN: 0305-1870 [Print] Australia
PMID8542678 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Adrenergic alpha-Agonists
  • Enzyme Inhibitors
  • Guanidines
  • Lipopolysaccharides
  • Arginine
  • Nitric Oxide Synthase
  • Acetylcholine
  • pimagedine
  • NG-Nitroarginine Methyl Ester
  • Norepinephrine
Topics
  • Acetylcholine (antagonists & inhibitors, pharmacology)
  • Adrenergic alpha-Agonists (pharmacology)
  • Animals
  • Aorta, Thoracic (drug effects)
  • Arginine (analogs & derivatives, antagonists & inhibitors, pharmacology)
  • Endothelium, Vascular (physiology)
  • Enzyme Inhibitors (pharmacology)
  • Guanidines (pharmacology)
  • In Vitro Techniques
  • Lipopolysaccharides (pharmacology)
  • Male
  • Muscle Relaxation (drug effects)
  • Muscle, Smooth, Vascular (drug effects)
  • NG-Nitroarginine Methyl Ester
  • Nitric Oxide Synthase (antagonists & inhibitors)
  • Norepinephrine (antagonists & inhibitors, pharmacology)
  • Rats
  • Rats, Sprague-Dawley

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