Capsaicin-induced gastric mucosal hyperemia and protection: The role of calcitonin gene-related peptide

Background. Topical capsaicin augments gastric mucosal blood flow and is cytoprotective. This phenomenon is blocked by nitric oxide (NO) synthase and cyclooxygenase inhibition. Capsaicin-sensitive neurons store and release calcitonin gene-related peptide (CGRP). The purpose of this investigation was to study the effects of a CGRP antagonist on capsaicin-induced hyperemia and protection and to determine the role of NO and the cytoprotective prostaglandin PGE₂ in this process. Methods. The glandular stomachs in male Sprague-Dawley rats (280 to 350 gm) were chambered with the blood supply intact. Animals were divided into four groups. Normal saline solution (group 1) or the CGRP antagonists hCGRP_8-37 (groups 2 through 4, 0.047 mg/ml) were continuously infused intraarterially via a retrograde splenic artery catheter at a rate of 0.034 ml/min after rats were given an intravenous bolus of either NSS (groups 1 and 2), L-arginine (group 3), or D-arginine (group 4) (200 mg/kg). The gastric mucosa was then topically exposed to normal saline solution (pH 7.4), followed by 160 μmol/L capsaicin and then 10 mmol/L acidified taurocholate (pH 1.2), each for 15 minutes. Gastric mucosal blood flow (ml/min/100 gm tissue) was continuously measured (laser Doppler) and mucosal injury was assessed. Luminal PGE₂ production was measured during the bile acid injury period by radioimmunoassay. Results. The CGRP antagonist hCGRP_8-37 significantly inhibits capsaicin-induced hyperemia and its associated mucosal cytoprotection and also significantly decreases luminal mucosal PGE₂ production. Pretreatment with L-arginine, but not D-arginine, reverses these effects of CGRP antagonism. Conclusions. CGRP is a mediator of capsaicin-induced hyperemia and protection. This effect may be dependent on both NO and PGE₂ production.