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(Circulation. 2007;115:1090-1100.)
© 2007 American Heart Association, Inc.

Heart Disease in Latin America

Sodium-Hydrogen Exchanger, Cardiac Overload, and Myocardial Hypertrophy

Horacio E. Cingolani, MD; Irene L. Ennis, MD

From the Centro de Investigaciones Cardiovasculares, Facultad de Ciencias Médicas, Universidad Nacional de La Plata, La Plata, Argentina.

Correspondence to Dr Horacio E. Cingolani, Centro de Investigaciones Cardiovasculares, Facultad de Ciencias Médicas, Universidad Nacional de La Plata, Calle 60 y 120, 1900 La Plata, Argentina. E-mail cicmes@infovia.com.ar

Received March 15, 2006; accepted August 30, 2006.

Key Words: hypertrophy • signal transduction • sodium

An extract of the first 250 words of the full text is provided, because this article has no abstract.

	Introduction

 
Overload of neonatal and adult cardiomyocytes and multicellular myocardial preparations, which include whole hearts, are accompanied by an enhanced activity of the Na⁺/H⁺ exchanger 1 (NHE-1). Exogenous administration of prohypertrophic agents such as angiotensin II (Ang II), endothelin-1 (ET-1), and ₁-adrenergic agonists also stimulates NHE-1 activity, which leads to an increased concentration of intracellular Na⁺ ([Na⁺]_i). Moreover, inhibition of NHE-1 activity prevents the increase in [Na⁺]_i, induces the regression of cardiac hypertrophy, and exerts beneficial effects in experimental heart failure.

The present review summarizes the current knowledge of the causative factors and pathophysiological correlation of cardiac overload and NHE-1 activity.

	The Na+/H+ Exchanger

 
NHE is an integral membrane glycoprotein expressed ubiquitously in mammalian cells, and it electroneutrally exchanges intracellular H⁺ for extracellular Na⁺ (1:1) to regulate intracellular pH (pH_i) and the concentration of [Na⁺]_i. Nine isoforms of this exchanger have been described: NHE-1 to NHE-9. NHE-1, the first isoform to be cloned, is expressed ubiquitously in the plasma membrane and is considered to be the cardiac-specific isoform.¹ The inward gradient of Na⁺, produced mainly by the Na⁺/K⁺ ATPase, provides a constant driving force for H⁺ extrusion and Na⁺ influx through the NHE.

NHE-1 (Figure 1) is a protein of 815 amino acid residues with a predicted molecular mass of 85 kDa that can be separated into an N-terminal membrane-associated domain (500 amino acid residues) and a long C-terminal cytoplasmic tail. The membrane domain, composed of 12 transmembrane regions, is associated . . . [Full Text of this Article]

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