title: Role of bradykinin in acid-induced mesenteric hyperemia and duodenal villous damage.
abstract: 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.
authors.affiliation: Research and Medical Services, Sepulveda Ambulatory Care Center and Nursing Home, Greater Los Angeles Healthcare System, Sepulveda, CA 91343, USA. felix.leung@wla.va.gov
authors.forename: Felix W
authors.initials: FW
authors.lastname: Leung
authors.forename: Fumihiro
authors.initials: F
authors.lastname: Iwata
authors.forename: John
authors.initials: J
authors.lastname: Kao
authors.forename: Kyoji
authors.initials: K
authors.lastname: Seno
authors.forename: Makoto
authors.initials: M
authors.lastname: Itoh
authors.forename: Joseph W C
authors.initials: JW
authors.lastname: Leung
mesh_terms: D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000502:physiology*; D065168:Bradykinin Receptor Antagonists; D002211:Capsaicin / Q000494:pharmacology; D004386:Duodenum / Q000187:drug effects / Q000473:pathology*; D006851:Hydrochloric Acid / Q000494:pharmacology; D006940:Hyperemia / Q000139:chemically induced / Q000503:physiopathology*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology; D008297:Male; D017538:Mesenteric Artery, Superior / Q000187:drug effects / Q000503:physiopathology; D008643:Mesentery / Q000187:drug effects / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018617:Ultrasonography, Doppler, Pulsed
chemical_list: D065168:Bradykinin Receptor Antagonists; C065679:icatibant; D006851:Hydrochloric Acid; D002211:Capsaicin; D001920:Bradykinin