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(Circulation Research. 2001;88:861.)
© 2001 American Heart Association, Inc.

Editorial

Renin-Angiotensin System in Human Failing Hearts

Message From Nonmyocyte Cells to Myocytes

Hiroaki Matsubara

From the Department of Medicine II and Cardiovascular Center, Kansai Medical University, Moriguchi, Osaka, Japan.

Correspondence to Hiroaki Matsubara, Department of Medicine II and Cardiovascular Center, Kansai Medical University, Moriguchi, Osaka 570-8507, Japan. E-mail matsubah@takii.kmu.ac.jp

Key Words: angiotensin II • angiotensin receptor • human heart • heart failure • angiotensin-converting enzyme

	Introduction

 
The survival benefit conferred by angiotensin-converting enzyme (ACE) inhibitors in patients with heart failure has led to an intense interest in the mechanisms underlying the action of angiotensin II.^{1 2} However, ACE inhibition therapy does not completely block angiotensin II production, and in some patients angiotensin II remains elevated, in part because of the conversion of angiotensin I to angiotensin II by chymase activity.³ The main two receptors for angiotensin II, AT₁ receptor (AT₁R) and AT₂ receptor (AT₂R), are present in the myocardium. Most angiotensin II functions in the cardiovascular system are mediated by AT₁R. AT₂R has anti-AT₁R effects, such as negative chronotropic action or inhibition of interstitial fibrosis, which may play a protective role in development of heart failure.⁴ Presently, no therapeutic agents that specifically act on AT₂R are approved for clinical trials. However, AT₁R blockers are available that could shunt the activity of the cardiac renin-angiotensin system toward selective stimulation of beneficial AT₂R. Two separate clinical approaches (ELITE-II and RESOLVD) compared ACE inhibitors with AT₁R blockers in patients with heart failure.^{5 6} No significant differences were observed in the beneficial effect of these two classes of agents, and the cardioprotective role of AT₂R remains to be determined.

The cardioprotective action of ACE inhibitors and AT₁R blockers depends on the expression level of myocardial AT₁R and AT₂R in patients with heart failure. The first study to examine these levels in human myocardium found no significant changes in total . . . [Full Text of this Article]

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