Inhibition of endogenous nitric oxide reduces basal mesenteric vascular tone but does not alter intraduodenal hydrochloric acid-induced intestinal hyperemia in rats

Abstract

There are conflicting reports on the role of endogenous nitric oxide (NO) in the regulation of basal intestinal blood flow. The effect of inhibition of NO on intraduodenal hydrochloric acid (HCl) induced intestinal hyperemia remains to be confirmed. We investigated the effect of inhibition of endogenous NO on basal intestinal blood flow, HCl-induced intestinal hyperemia, and duodenal villous injury. Superior mesenteric artery blood flow in rats was measured by pulsed Doppler flowmetry and duodenal villous injury evaluated by histology. Intravenous N^G-nitro-l-arginine methyl ester (l-NAME), orl-arginine ord-arginine followed byl-NAME, was given to show inhibition, reversal of inhibition of endogenous NO synthase, and stereospecificity, respectively. An intraduodenal 2 ml/kg bolus or perfusion for 30 min of 0.1 N HCl was given 15 min afterl-NAME or vehicle. Mean arterial blood pressure was increased byl-NAME, which also significantly reduced intestinal blood flow under basal condition and after intraduodenal HCl. Basal mesenteric blood flow was not altered byl- ord-arginine. Thel-NAME-induced increase in blood pressure and decrease in basal blood flow was attenuated byl- but notd-arginine. The villous damage and the magnitude of the peak hyperemia was unchanged byl-NAME,l- ord-arginine. Inhibition of endogenous NO byl-NAME is suggested by the significant rise in blood pressure. The rise in blood pressure and reduction in blood flow are attenuated byl- but notd-arginine, indicating stereospecificity. Inhibition of endogenous NO reduces basal mesenteric vascular tone but does not alter intraduodenal HCl-induced intestinal hyperemia. The increase in blood flow after intraduodenal HCl predicts the absence of exacerbation of HCl-induced duodenal villous damage.