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 vascular 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 nitric 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 lipopolysaccharide 20 mg/kg. Subgroups were given either aminoguanidine or L-NAME.

MAIN OUTCOME MEASURES

After 4 hours, isolated perfused mesenteric preparations were obtained and pressor responses to phenylephrine and vasodilatation responses to acetylcholine were evaluated, and plasma nitrite concentrations measured.

RESULTS

Pressor 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, aminoguanidine and L-NAME did not alter the vascular reactivity. The baseline plasma nitrite concentrations in the control group were increased 5-fold during endotoxaemia. This increase was significantly reduced with aminoguanidine but not with L-NAME.

CONCLUSION

The protection achieved by aminoguanidine but not L-NAME suggested that nitric oxide produced by inducible nitric oxide synthase had a role in the impairment of endothelial response during endotoxaemia, and confirmed the importance of selective inducible nitric oxide synthase inhibition to achieve beneficial effects in endotoxaemia.