In ischemia/reperfusion, mast cells can release renin initiating activation of local renin-angiotensin system, ultimately leading to the production of angiotensin II and norepinephrine (NE) and mediating severe arrhythmic dysfunction. Morrey et al. set out to determine whether neuropeptides released from sensory nerve cells during ischemia/reperfusion were responsible for the release of renin from mast cells. Sensory nerves are juxtaposed to cardiac mast cells, and stimulation of sensory C-fibers releases calcitonin gene-related peptide (CGRP) and substance P, which in turn is accompanied by an overflow of renin and NE. The release of renin and NE is prevented by mast cell stabilizers and pharmacological blockage of substance P and CGRP receptors; whereas NE release is blocked by an angiotensin receptor (AT1) antagonist that itself does not prevent the release of renin. Coupled to the in vitro ability of substance P to elicit mast cell renin release and that ischemia/reperfusion elicits substance P and CGRP release followed by renin and NE, which is accompanied by sustained reperfusion arrhythmias, supports the hypothesis that in the heart the link between sensory C-fibers and cardiac mast cells is the release of neuropeptides.
See article at J Pharmacol Exp Ther 2010, 335:76–84.
- Copyright © 2010 by The American Society for Pharmacology and Experimental Therapeutics