Detrimental effects of nitric oxide on mesenteric circulation during endotoxaemia and its reversal by aminoguanidine

Objective: To investigate the effect of endotoxaemia on rat mesenteric vasc ular bed and plasma nitrite concentrations, the possible beneficial effect of aminoguanidine (the selective inducible nitric oxide synthase inhibitor) compared with N-G-nitro-L-arginine methyl ester (L-NAME) (non-selective ni tric oxide synthase inhibitor). Design: Randomised experiment. Setting. University surgical research laboratory, Turkey. Subjects: 75 Wistar rats. Interventions: Rats were divided into control (n = 30) and endotoxaemia (n = 42) groups. Endotoxaemia was produced by intraperitoneal injection of lip opolysaccharide 20 mg/kg. Subgroups were given either aminoguanidine or L-N AME. Main outcome measures: After 4 hours, isolated perfused mesenteric preparat ions were obtained and presser responses to phenylephrine and vasodilatatio n responses to acetylcholine were evaluated, and plasma nitrite concentrati ons measured. Results: Presser response to phenylephrine did not alter but vasodilatation in response to acetylcholine was significantly reduced during endotoxaemia . Pretreatment with aminoguanidine prevented the impairment of the response to acetylcholine. However, L-NAME was ineffective. in the control group, a minoguanidine and L-NAME did not alter the vascular reactivity. The baselin e plasma nitrite concentrations in the control group were increased 5-fold during endotoxaemia. This increase was significantly reduced with aminoguan idine but not with L-NAME. Conclusion: The protection achieved by aminoguanidine but not L-NAME sugges ted that nitric oxide produced by inducible nitric oxide synthase had a rol e in the impairment of endothelial response during endotoxaemia, and confir med the importance of selective inducible nitric oxide synthase inhibition to achieve beneficial effects in endotoxaemia.