Effects of aminoguanidine and N(omega)-nitro-L-arginine methyl ester on vascular hyporeactivity induced by endotoxaemia.Eur J Surg. 2001 Nov; 167(11):803-9.EJ
To investigate the effects of endotoxaemia on the reactivity of the aortic bed in rats, and to compare the effects of the nitric oxide (NO) synthase inhibitors aminoguanidine and N(omega)-nitro-L-arginine methyl ester (L-NAME), on endotoxaemia-induced changes in vascular reactivity.
University laboratory, Turkey.
54 Wistar rats.
Rats were divided into control (n = 24) and endotoxaemia (n = 30) groups and were treated with an intraperitoneal injection of saline (control) and lipopolysaccharide (20 mg/kg), respectively. Subgroups of control and endotoxaemic rats were given either aminoguanidine or L-NAME by the same route.
MAIN OUTCOME MEASURES
Contractile responses to phenylephrine and relaxation responses to acetylcholine 4 hours after treatment.
Incubation with aminoguanidine and L-NAME potentiated the phenylephrine-induced contractile response and inhibited acetylcholine-induced relaxation in aortic rings in the control group. The vascular responses to phenylephrine and acetylcholine were less pronounced in the endotoxaemia group, and in vitro incubation with aminoguanidine and L-NAME partially restored the contraction induced by phenylephrine but did not affect the impaired response to acetylcholine. Aminoguanidine given in vivo prevented the impairment of vascular responses to both phenylephrine and acetylcholine whereas L-NAME gave no such protection.
Aminoguanidine acted similarly to L-NAME when incubated with the tissues in vitro, and did not show selectivity to inducible compared with constitutive isoforms of NO synthase. The finding that aminoguanidine but not L-NAME, prevented the endotoxin-induced impairment of vascular reactivity when administrated in vivo, therefore, suggested a role other than inhibition of NO synthase.