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COMPARISON OF RESPONSES TO AMINOGUANIDINE AND N ω ‐NITRO‐L‐ARGININE METHYL ESTER IN THE RAT AORTA
Author(s) -
Yen MaoHsiung,
Chen ShiuJen,
Wu ChinChen
Publication year - 1995
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.1995.tb02081.x
Subject(s) - nitric oxide , chemistry , nitric oxide synthase , arginine , endocrinology , medicine , norepinephrine , aorta , acetylcholine , nitro , contraction (grammar) , in vivo , biochemistry , biology , amino acid , alkyl , microbiology and biotechnology , organic chemistry , dopamine
SUMMARY 1. We have compared the effect of aminoguanidine with that of N ω ‐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 3h resulted in a hypo tension and a significant reduction of pressor responses to nor‐epinephrine (1 μg/kg, i.v.) in the anaesthetized rat. 3. In intact rings obtained from vehicle treated rats, amino guanidine (0.3 and 1mmol/L) had no significant effect on acetylcholine‐induced relaxation (10 ‐9 –10 ‐5 mol/L), whereas N ω ‐nitro‐L‐arginine methyl ester (0.3mmol/L and 1mmol/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 ω ‐nitro‐L‐arginine methyl ester (0.3 mmol/L) in endo thelium‐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 ω ‐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 ω ‐nitro‐L‐arginine methyl ester is a non‐selective inhibitor of both the inducible and constitutive nitric oxide synthase.