Calcitonin-gene related peptide can augment or prevent endothelin-1 induced gastric microvascular leakage

The effects of locally infused calcitonin gene-related peptide (CGRP) on the changes in microvascular permeability and tissue injury following close-arterial infusion of endothelin-1 (5 pmol kg-1 min-1, 10 min) in the rat gastric mucosa have been investigated. Pretreatment with rat alpha-CGRP (10-50 pmol kg-1 min-1) inhibited the leakage of radiolabelled albumin and reduced the haemorrhagic necrosis, an action inhibited by the CGRP receptor antagonist, hCGRP-(8-37) (2 nmol kg-1 min-1). By contrast, local infusion of CGRP immediately following endothelin-1 challenge had no such protective actions, and significantly exacerbated the microvascular leakage and tissue injury at the higher dose. These studies suggest that CGRP can exert both pro- and anti-inflammatory actions in the gastric microcirculation.