Action of angiotensin II on the isolated intact heart

Current data support an angiotensin (Ang) II-forming pathway in the heart. The expression of angiotensinogen, angiotensin-converting enzyme (ACE), angiotensin receptors (AT₁ and AT₂), and renin has been demonstrated on both mRNA and protein levels, and a number of actions have been related to activation of this local renin-angiotensin system in the heart. Although the final physiological and pathophysiological role of the cardiac renin- angiotensin system remains to be determined, there is growing evidence that local production of Ang II is of functional importance. Specifically, studies in isolated working hearts helped to separate the effects of the local and systemic renin-angiotensin systems. For example, some pharmacological effects of ACE inhibitors are sustained in isolated hearts even in the absence of any circulating component of the renin-angiotensin system. Thus, data from isolated hearts suggest a significant contribution of the tissue renin- angiotensin system to cardiac effects or, vice versa to the pharmacological action of its inhibitors. These effects may include the induction of cardiac myocyte growth, coronary vasoconstriction, positive inotropy, and negative lusitropy, as well as postischemic reperfusion arrhythmias and injuries. The local renin-angiotensin system of the heart has been investigated extensively. This article will focus on studies of this system, which have been performed in isolated beating hearts.