In this issue of the JCI, Mackins, Levi, and associates show that ischemia of the heart triggers renin release by cardiac mast cells, resulting in activation of the RAS (11). The consequent production of angiotensin II stimulates angiotensin II receptor, type 1 (AT₁) in sympathetic nerve terminals, causing release of norepinephrine (NE) and generation of cardiac arrhythmias. These studies indicate that resident mast cells in the heart and perhaps other organs, upon appropriate stimulation, are capable of producing ample quantities of renin to activate the RAS locally and thereby modulate organ function. This pathway is likely to be regulated by factors linked to inflammation and injury that are quite different from those controlling renin release at the JG apparatus of the kidney. NHE, Na⁺/H⁺ exchanger.