Acid-induced mesenteric hyperemia in rats - Role of CGRP, substance P, prostaglandin, adenosine, and histamine

Intraduodenal acidification produces a mesenteric hyperemia that is mediated in part by mucosal capsaicin- sensitive afferent nerves and the bradykinin B-2 receptor in anesthetized rats. We hypothesized that novel mechanisms mediated by substance P, adenosine, and histamine(1) receptors are involved. Confirmation of a role for calcitonin gene- related peptide (CGRP) but not endogenous prostaglandin was also sought. In study 1, vehicle or antagonists (CGRP(8- 37), CP 96345) was administered intravenously. Capsaicin or acid was administered intraduodenally, followed by intravenous CGRP or substance P. In study 2, pretreatments included indomethacin, 8- phenyltheophylline, pyrilamine, or the respective vehicles. Acid was then administered intraduodenally. In both studies, superior mesenteric artery blood flow was monitored. In study 1, the antagonists significantly attenuated capsaicin- and acid- induced mesenteric hyperemia. In study 2, the pretreatments did not alter acid- induced hyperemia. The data confirmed the role of CGRP and indicated for the first time an involvement for substance P in acid- induced mesenteric hyperemia.