1. Cardiac Production of Angiotensin II and Its Pharmacologic Inhibition: Effects on the Coronary Circulation 
Axel Schmermund, M.D., Lilach O. Lerman, M.D., Ph.D., Erik L. Ritman, M.D., Ph.D., John A. Rumberger, Ph.D., M.D. 
Mayo Clinic Proceedings 
Volume 74, Issue 5, Pages (May 1999)
DOI: /
Copyright © 1999 Mayo Foundation for Medical Education and Research Terms and Conditions

2. Fig. 1
Overview of renin-angiotensin system under physiologic conditions (A) and during angiotensin-converting enzyme (ACE) inhibition (B) or specific angiotensin receptor blockade (C). A, Physiologic conditions. Kidney-derived renin catalyzes formation of angiotensin I (AI) from angiotensinogen. Angiotensin II (AII) is cleaved from AI by ACE activity. AII acts through specific receptors (angiotensin receptor subtypes 1 and 2 [AT1], AT2]) expressed in arterial intima and media and various other tissues not shown. These receptors mediate direct actions of AII such as vasoconstriction, but they also release other factors involved in actions of AII; among these are bradykinin and, not shown in figure, endothelin. Bradykinin is cleaved from kininogen by kallikrein and deactivated mainly by kininase II. Kininase II is identical with ACE, which thus not only catalyzes formation of All but also degradation of bradykinin. Through specific receptors (bradykinin receptor subtype 2 [B2]), bradykinin exerts vasodilator actions through pathways involving endotheliumderived nitric oxide (NO) (“relaxing factor”) and prostaglandins (PG) such as prostacyclin and prostaglandin E2. B,Effects of ACE inhibition. Because of inhibition of ACE, activity of AII is markedly reduced. Al accumulates, and because of low All activity, renal renin production is up-regulated. Concentrations of AII and renin are therefore increased (blue letters). Because of inhibition of kininase II, which is identical to ACE, bradykinin levels are also increased and consequently NO and certain PG. C, Effects of specific All receptor subtype I blockade. Coupling of AII to its AT1 receptors is blocked. AII and AI accumulate, and renal renin production is up-regulated (blue letters). Enhanced concentrations of All result in an increase release of bradykinin mediated probably by the AT2 receptor subtype.
Mayo Clinic Proceedings  , DOI: ( / )
Copyright © 1999 Mayo Foundation for Medical Education and Research Terms and Conditions