Involvement of nitric oxide in mesenteric vascular reactivity following intraperitoneal pancreatic juice in rats.

The purposes of this study were to examine the protein expressions of endothelial and inducible nitric oxide synthase (eNOS and iNOS) of the rat intestinal smooth muscle, and to elucidate the role of nitric oxide (NO) in the reactivity of the superior mesenteric artery (SMA) to vasoconstrictors following intraperitoneal (i.p.) injection of pancreatic juice. Immunohistochemistry was used to observe the protein expressions of eNOS and iNOS in the intestinal tissues 15 h after i.p. injection of pancreatic juice (1 ml/100 g body weight). To test the vascular reactiveness, SMA was isolated and perfused with Tyrode's solution at a constant flow rate of 5 ml/min. The changes in perfusion pressure as the measure of contractile responses to phenylephrine (PE) were monitored. I.P. injection of pancreatic juice induced increases of plasma levels of tumor necrosis factor α (TNFα) (P < 0.001; N = 7) and NO (P < 0.001; N = 7). Nω-nitro-L-arginine methyl ester (L-NAME) reduced the release of TNFα and NO. There were 8.3 ± 1.2-fold and 11.4 ± 2.8-fold increases in the protein expressions of eNOS and iNOS, respectively, in the intestinal tissue after pancreatic juice injection. PE (10⁻⁸ ~ 10⁻⁴ M) produced a dose-dependent vasoconstrictive effects on the SMA bed. Contractile responses to PE were attenuated in pancreatic juice-treated group. Addition of L-NAME (10⁻⁴ M) resulted in full recovery of the responses to phenylephrine in SMA bed, while aminoguanidine (AG, 10⁻⁴ M) caused only partial recovery. Our results indicate that i.p. injection of pancreatic juice results in a decrease in vascular reactivity of mesenteric vessels that is dependent on both eNOS and iNOS expressions in the intestinal vascular bed. Overproduction of NO elicits intestinal low vascular reactivity.