The beneficial effects of renin-angiotensin system blockers on cardiac structure and function are usually explained based on the capacity of these drugs to interfere with angiotensin II at cardiac tissue sites. This review addresses to what degree cardiac angiotensin II generation occurs independently of the circulating renin-angiotensin system, and in particular tries to unravel where such generation might take place, taking into consideration that many reports suggest that angiotensin II is an intracrine hormone (ie, a hormone that is synthesized and acts intracellularly). It concludes that angiotensin II generation in the heart depends on circulating (ie, kidney-derived) renin, and occurs in interstitial fluid and possibly, in view of the recent discovery of renin-binding sites, on the cell surface of cardiac cells. Intracellular angiotensin II generation is unlikely to occur, in particular because angiotensinogen is not available in the cytosol.

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American Journal of Hypertension
Department of Pharmacology