Role of Calcitonin Gene-related Peptide in Gastric Hyperemic Response to Intragastric Capsaicin

Stimulation of sensory neurons in the rat stomach by intragastric capsaicin leads to a marked rise in gastric mucosal blood flow (GMBF). The gastric mucosa, in particular submucosal blood vessels, is densely innervated by afferent neurons containing peptides, of which calcitonin gene-related peptide (CGRP) is the most potent vasodilator. Using selective ablation of either the vagal or spinal sensory innervation to the stomach by perineural application of capsaicin, and by intra-arterial infusion of the CGRP receptor antagonist hCGRP-(8-37) close to the stomach, we investigated 1) the origin (vagal or spinal) of the sensory neurons and 2) whether CGRP mediates this hyperemic response. Perivagal application of capsaicin to the rat 10-20 days before experiments had no effect on the hyperemic response to intragastric capsaicin. In contrast, periceliac application of capsaicin significantly reduced this response by 60%. Intra-arterial infusion of CGRP (20 pmol/min) close to the stomach produced a marked rise in GMBF and this was completely blocked by hCGRP-(8-37) (500 pmol/min). intra-arterial infusion of hCGRP-(8-37) or its vehicle, bovine serum albumin, had no significant effect on basal GMBF. However, the increment in GMBF in response to intragastric capsaicin was significantly attenuated by 79%. We conclude that 1) spinal sensory neurons innervating the gastric mucosa partially mediate the increase in GMBF induced by intragastric capsaicin and 2) CGRP is the major vasodilator released by these fibers.