COMPARISON OF RESPONSES TO AMINO GUANIDINE 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 obtain ed 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 presser re sponses to norepinephrine (1 mu g/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 met hyl ester (0.3 mmol/L and 1 mmol/L) abolished that response, suggestin g that aminoguanidine does not inhibit the activity of constitutive ni tric 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 endotheli um-denuded aortic rings obtained from endotoxin treated rats. 5. Three hours of endotoxaemia was associated with an impairment of contractio n to norepinephrine (10(-9)-10(-6) mol/L) in the endothelium-denuded a orta ex vivo, This hyporeactivity to norepinephrine was partially rest ored 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 th at aminoguanidine is a selective inhibitor of the inducible nitric oxi de synthase, whereas NO-nitro-L-arginine methyl ester is a non-selecti ve inhibitor of both the inducible and constitutive nitric oxide synth ase.