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(Circulation. 2001;104:247.)
© 2001 American Heart Association, Inc.

Editorials

AT₂, Judgment Day

Which Angiotensin Receptor Is the Culprit in Cardiac Hypertrophy?

Michael D. Schneider, MD; Beverly H. Lorell, MD

From the Center for Cardiovascular Development, Baylor College of Medicine, Houston, Tex (M.D.S.), and the Cardiology Division, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Mass (B.H.L.).

Correspondence to Dr Michael D. Schneider, Center for Cardiovascular Development, Baylor College of Medicine, One Baylor Plaza, Room 506C, Houston, TX 77030. E-mail michaels@bcm.tmc.edu

Key Words: Editorials • angiotensin • cardiac hypertrophy • gene targeting • mice • receptor

As reviewed recently in these pages,¹ the vasoconstrictor angiotensin II (Ang II) is one of the circulating peptide growth factors, and clinically the most relevant, that fulfill many of Koch’s postulates for having additional effects locally in the myocardium. These criteria include local production of Ang II within the heart, its upregulation there by hypertrophic signals, its release from cardiac cells after mechanical load, the presence of its receptors on the surface of cardiac cells, and the responsiveness of both cardiac myocytes and cardiac fibroblasts to provocation by this peptide.^1,2 This local circuit of Ang II production, release, binding, and transduction within the myocardium itself is the most cogent explanation for the effectiveness of ACE inhibitors in heart failure, even at doses that do not alter loading conditions.^1,2

See p 346

Three related receptors exist for Ang II: AT_1a, AT_1b, and AT₂, which communicate with a complex cell-wide web of signaling cascades through GTP-binding (G) proteins as the proximal transducer. The operation of a local circuit for Ang II within the myocardium poses two questions, which have attracted much recent experimental effort, and an even larger share of controversy. First, given that multiple receptors exist for Ang II, which type or types are responsible for pathobiology provoked by the local circuit? Second, given that cardiac muscle and nonmuscle cells are both potential targets for Ang II, what is the respective role of each?

Genetic models that altogether lack the receptors individually provide an invaluable experimental tool beyond . . . [Full Text of this Article]

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