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(Circulation Research. 1999;85:658-660.)
© 1999 American Heart Association, Inc.

Editorial

A Role for the Sarcolemmal Na⁺/H⁺ Exchanger in the Slow Force Response to Myocardial Stretch

Jonathan C. Kentish

From the Centre for Cardiovascular Biology & Medicine, King's College London, London, UK.

Correspondence to Dr J.C. Kentish, Centre for Cardiovascular Biology & Medicine, King's College London, The Rayne Institute, St Thomas' Hospital, London, SE1 7EH, UK. E-mail jon.kentish@kcl.ac.uk

Key Words: Na⁺/H⁺ exchanger • stretch • Anrep effect • angiotensin II • endothelin

	Introduction

 
Although the contractile performance of the myocardium is under continuous nervous and hormonal regulation, the myocardium possesses a number of intrinsic, load-dependent mechanisms by which it can adjust cardiac output to meet the needs of the circulation over periods ranging from seconds to years. In isolated hearts, an increase in ventricular end-diastolic volume (EDV), produced by increased venous return or decreased aortic outflow, leads immediately to a more powerful contraction via the Frank-Starling mechanism ("heterometric autoregulation"¹ ), so that cardiac output increases over a few beats to match venous return. However, over the next few minutes, there is a further increase in myocardial performance, such that EDV returns toward its original value. This second autoregulatory mechanism, the "Anrep effect"² or "homeometric autoregulation,"¹ allows a given change in cardiac output to be achieved with a smaller change in EDV than if the Frank-Starling effect were the only compensatory mechanism. Finally, if the increase in EDV or wall stress is maintained, genes are switched on that eventually lead to myocardial cell hypertrophy.

Much is known about the cellular and molecular basis of the Frank-Starling mechanism and of the initial stages of load-induced hypertrophy, but the processes responsible for the Anrep effect are poorly understood. In this issue of Circulation Research, Alvarez et al³ suggest a novel mechanism for the slow increase in myocardial contractility: a stretch-induced activation of the sarcolemmal Na⁺/H⁺ exchanger (NHE) by local autocrine/paracrine systems involving angiotensin II (Ang II) and endothelin-1 (ET-1).

	The Contractile Response to Stretch of the Myocardium

 
Our knowledge of the cellular . . . [Full Text of this Article]

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