Protective effects of nitroglycerin-induced preconditioning mediated by calcitonin gene-related peptide in rat small intestine

Previous studies of myocardium have shown that ischemic preconditioning could be mimicked by nitroglycerin through stimulating the release of calcitonin gene-related peptide (CGRP). The present study examined whether nitroglycerin could also provide a preconditioning stimulus in the peripheral vascular bed (the anse intestinalis of rat), and whether endogenous CGRP is involved in this process. The model of in situ perfusion was prepared with rat small intestine. One hour of ischemia and 15 min of reperfusion caused a significant impairment of intestinal morphology and an increase in the release of both lactate dehydrogenase and malondialdehyde. Pretreatment with nitroglycerin, 10(-7), 3 X 10(-7), 10(-6) M for 5 min produced a significant improvement of intestinal tissue morphology and a decrease in the release of both lactate dehydrogenase and malondialdehyde. However, the protection afforded by nitroglycerin was abolished by CGRP-(8-37), a selective CGRP acceptor antagonist. Pretreatment with capsaicin, which specifically depletes the transmitter content of sensory nerves, also abolished the protection by nitroglycerin. In addition, the content of CGRP-like immunoreactivity in the effluent was increased during nitroglycerin perfusion. On the other hand, the results from the in vivo experiment showed that nitroglycerin (i.v. 0.13 m/kg injected 5 min before prolonged ischemia could provide significant protection against the injury caused by 30-min ischemia and 1-h reperfusion in the rat small intestine, but would also cause a significant increase in the levels of CGRP in the plasma. All these findings suggest that nitroglycerin-induced preconditioning is related to stimulation of CGRP release in the rat small intestine. (C) 2001 Elsevier Science B.V. All rights reserved.