Renin released by ischemia/reperfusion (I/R) from cardiac mast cells (MC) activates a local renin-angiotensin system (RAS) causing arrhythmic dysfunction. Ischemic preconditioning (IPC) inhibits MC renin release and consequent activation of this local RAS. The present study found that activation of MC histamine H4-receptors (H4R) mimics the cardioprotective anti-RAS effects of IPC and that protection depends on the sequential activation of protein kinase C isotype-ε and aldehyde dehydrogenase type-2 in MC, reducing aldehyde-induced MC degranulation and renin release and alleviating reperfusion arrhythmias. These cardioprotective effects disappear when H4R are pharmacologically blocked or genetically deleted. This newly discovered protective pathway suggests that MC H4R may represent a new pharmacologic and therapeutic target for the direct alleviation of RAS-induced cardiac dysfunctions, including ischemic heart disease and congestive heart failure.
See article at J Pharmacol Exp Ther 2014, 349:508–517.
- Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics