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 B2 receptor in anesthetized rats. We hypothesized that novel mechanisms mediated by substance P, adenosine, and histamine1 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.

Ruthenium red-sensitive cation channels, but not calcitonin gene-related peptide or substance P-mediated mechanisms, protect duodenal villi against acid-induced damage.

Intestinal mucosal capsaicin-sensitive afferent nerves mediate, in part, the protective mesenteric hyperemia after intraduodenal acidification. Mechanisms associated the sensory neuropeptides, e.g. calcitonin gene-related peptide (CGRP), substance P, and ruthenium red-sensitive cation channels contribute to acid-induced mesenteric hyperemia, but whether they play a role in protection against acid-induced duodenal villous damage is not known. We tested the hypothesis that in doses that attenuate acid-induced hyperemia, inhibitors of these mechanisms will exacerbate acid-induced duodenal villous damage. Intravenous vehicle, specific receptor antagonists of CGRP (CGRP(8-37)), substance P (CP 96345), intraduodenal ruthenium red or vehicle was administered, followed by intraduodenal perfusion with 0.1 N HCl. Duodenal tissue was processed for hematoxylin and eosin staining. Villous damage was scored by blinded observers. Deep villous injury was significantly increased after treatment with ruthenium red, but not with CGRP(8-37) or CP 96345. These findings support the hypothesis that ruthenium red-sensitive cation channels, but not neuropeptides associated with intestinal mucosal afferent nerves, are involved in the acid-sensing mechanism which mediates the protection against acid-induced duodenal villous damage.

Tonsillar tuberculosis associated with pulmonary and laryngeal foci.

Tonsillar tuberculosis is one of the uncommon forms of extrapulmonary tuberculosis. We report a case of tonsillar tuberculosis associated with pulmonary and laryngeal foci. A 23-year-old female was admitted for evaluation of hoarseness and difficulty in swallowing. Bilateral palatine tonsils were enlarged, and a tonsillectomy was performed. Since a histological study revealed tonsillar tuberculosis, antituberculous agents were administered. After the treatment the pulmonary lesions detected with chest computed tomography were improved, and her symptoms were relieved. The possibility of tonsillar tuberculosis should be considered when unexplained enlarged tonsil is observed in patients with pulmonary tuberculosis.

Role of bradykinin in acid-induced mesenteric hyperemia and duodenal villous damage.

Intestinal mucosal capsaicin-sensitive afferent nerves mediate, in part, the mesenteric hyperemia after intraduodenal acidification. The hyperemia plays a role in protecting the duodenal mucosa against acid damage. We tested the hypothesis that bradykinin contributes to this protective hyperemia. A specific antagonist of bradykinin will attenuate the hyperemia and exacerbate duodenal villous damage induced by acid. Study 1: Intravenous vehicle, or the specific bradykinin B2 receptor antagonist (HOE 140) was administered to anesthetized rats. This was followed by intraduodenal bolus administration of 160 microM capsaicin or 0.1 N HCl, and then intravenous bradykinin. Study 2: Intravenous administration of vehicle or HOE 140 was followed by duodenal perfusion with 0.1 N HCl. Superior mesenteric artery blood flow (pulsed Doppler flowmetry) (Study 1) and duodenal villous damage (histology) (Study 2) were recorded. HOE 140 significantly reduced the hyperemia induced by bradykinin and intraduodenal capsaicin or acid. Deep villous injury was significantly increased after treatment with HOE 140. These findings support the hypothesis that acid-induced and afferent nerve-mediated mesenteric hyperemia is modulated by a mechanism that involves bradykinin B2 receptor. Antagonism of bradykinin B2 receptor also increased acid-induced deep duodenal villous damage. Thus, maintenance of bradykinin-mediated mesenteric hyperemia, is a previous unrecognized mechanism associated with protection of the rat duodenal mucosa against acid-induced damage.