MECHANISM OF ACID-INDUCED MESENTERIC HYPEREMIA IN RATS

The mesenteric hyperemia induced by intraduodenal application of hydro chloric acid (HCl) is mediated in part by capsaicin-sensitive afferent nerves. Antagonist of capsaicin-sensitive receptors (capsazepine) and blocker of capsaicin-sensitive cation channels (ruthenium red) have b een described. We employed these tools to dissect the mechanism of reg ulation of mesenteric hyperemia induced by intraduodenal administratio n of HCl. Subcutaneous 100 mu mol/kg capsazepine or intraduodenal 0.1% ruthenium red was administered to pentobarbital anesthetized rats. Th en, 2.5 ml/kg of 640 mu M capsaicin or 0.1 N HCl was administered intr aduodenally. The mesenteric hyperemic responses were recorded. The res ults demonstrated that in a dose that decreased the mesenteric hyperem ia induced by intraduodenal capsaicin, capsazepine failed to attenuate the mesenteric vasodilatory effect of intraduodenal HCl. Ruthenium re d significantly attenuated the mesenteric hyperemia after intraduodena l capsaicin and HCl. These in vivo data provide the first functional e vidence for the existence of capsazepine-sensitive capsaicin receptors and cation channel complexes in the rat duodenal and intestinal mucos a. The capsaicin- and HCl-sensitive receptors are unlikely to be funct ionally identical in these locations. The ruthenium red-sensitive cati on channels appear to mediate the capsaicin- and HCl-induced mesenteri c hyperemia.