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.
Leung
Felix W
FW
Research and Medical Services, Sepulveda Ambulatory Care Center and Nursing Home, Veterans Affairs Greater Los Angeles Healthcare System, Sepulveda, California 91343, USA.
Iwata
Fumihiro
F
Seno
Kyoji
K
Leung
Joseph W C
JW
D000241:Adenosine / Q000502:physiology*; D000818:Animals; D001783:Blood Flow Velocity; D001794:Blood Pressure; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology / Q000502:physiology; D002211:Capsaicin / Q000494:pharmacology; D006851:Hydrochloric Acid / Q000494:pharmacology; D006940:Hyperemia / Q000139:chemically induced / Q000503:physiopathology*; D007413:Intestinal Mucosa / Q000502:physiology; D017078:Laser-Doppler Flowmetry; D008297:Male; D017538:Mesenteric Artery, Superior / Q000503:physiopathology*; D008643:Mesentery / Q000098:blood supply*; D009419:Nerve Tissue Proteins / Q000502:physiology*; D011453:Prostaglandins / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011969:Receptors, Histamine H1 / Q000502:physiology*; D012039:Regional Blood Flow / Q000502:physiology; D013373:Substance P / Q000494:pharmacology / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology
D009419:Nerve Tissue Proteins; D011453:Prostaglandins; D011969:Receptors, Histamine H1; D014665:Vasodilator Agents; D013373:Substance P; D015740:Calcitonin Gene-Related Peptide; D000241:Adenosine; D006851:Hydrochloric Acid; D002211:Capsaicin