COMPARISON OF RESPONSES TO AMINOGUANIDINE AND Nω‐NITRO‐L‐ARGININE METHYL ESTER IN THE RAT AORTA

Publisher Website
Google Scholar
Abstract
SUMMARY: 1. We have compared the effect of aminoguanidine with that of Nω‐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 (10‐9–10‐5mol/L), whereas Nω‐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 (10‐6–10‐2mol/L) was competitively inhibited by both aminoguanidine (0.3 mmol/L) and Nω‐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 Nω‐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 Nω‐nitro‐L‐arginine methyl ester is a non‐selective inhibitor of both the inducible and constitutive nitric oxide synthase.