Aminoguanidine attenuates endotoxin-induced mesenteric vascular hyporeactivity

Background: The aim of this study was to investigate the effects of inducib le nitric oxide synthase inhibition by aminoguanidine on endotoxin-induced reduction in mesenteric blood flow. Methods: Twenty Sprague-Dawley rats (180-230 g) allocated into four groups were administered either Escherichia coli endotoxin 1 mg/kg intraperitoneal ly or its solvent saline and were pretreated with either aminoguanidine (15 mg/kg intraperitoneally 20 min before and 2 h after endotoxin injection) o r saline. Some 4 h after endotoxin injection, animals were anaesthetized, a rterial blood pressure and mesenteric blood flow were measured and the resi stance in the mesenteric vascular beds was then calculated. The effect of p henylephrine (1-30 mu g/kg intravenously) on these parameters was also inve stigated. Results: Endotoxin did not significantly modify the mean arterial blood pre ssure but decreased mesenteric blood flow by increasing the vascular resist ance (mean(s.e.m.) 7.8(1.0) versus 13.7(1.2) mmHg per min per ml for contro l versus endotoxin groups; n = 5, P = 0.0099). Aminoguanidine alone had no effect on either the mean arterial blood pressure or mesenteric blood flow, but it completely blocked the effects of endotoxin. On the other hand, end otoxin significantly attenuated the responsiveness to phenylephrine which w as restored by aminoguanidine. Conclusion: The present results indicate that endotoxin decreases the mesen teric vascular blood flow by increasing vascular resistance and decreases r esponsiveness to phenylephrine. The effects of endotoxin were inhibited by aminoguanidine. The mesenteric vasoconstriction in response to endotoxin mi ght not be explained by the overproduction of nitric oxide; other actions o f aminoguanidine may explain its inhibitory effect.