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(Circulation Research. 2002;90:751.)
© 2002 American Heart Association, Inc.

Editorials

Na⁺-H⁺ Exchanger Inhibition

A New Antihypertrophic Tool

Horacio E. Cingolani, María Cristina Camilión de Hurtado

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

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

Key Words: Na⁺-H⁺ exchanger • cardiac hypertrophy • NHE1 inhibitors

Cardiac hypertrophy (CH) is a major risk factor for cardiac death and commonly precedes the development of heart failure (HF). This is motivating the search for novel pharmacological strategies to prevent the development and/or regress CH. Although the signaling pathways leading to myocardial hypertrophy are complex, one important set of pathways involves the mitogen-activated protein kinases (MAPKs).¹ MAPKs phosphorylate numerous substrates, including nuclear transcription factors that activate the expression of different genes. The Na⁺-H⁺ exchanger (NHE) is a common downstream effector of this cascade^2–4 and has been implicated in different models of hypertrophy, such as "hypertensive" myocardium, aortic constriction-induced hypertrophy, and postinfarction myocardial hypertrophy.^5–8 Interestingly, stretch-induced hypertrophy of cultured neonatal cardiomyocytes is also accompanied by an increase in MAPK activity^6,8 and NHE activation. Furthermore, stretch-induced MAPK stimulation is partially prevented by inhibition of NHE activity.⁶

The article published in this issue of Circulation Research by Engelhardt et al⁹ reports another example of a link between NHE activity and cellular growth, employing a different experimental model of CH induced by overexpression of ß₁-adrenergic receptors in transgenic mice. CH, fibrosis, and failure induced by this model were prevented by NHE inhibition. The overstimulation of ß₁-adrenergic receptors with isoproterenol is perhaps a similar experimental model of hypertrophy that has been extensively studied before^10–13 and reported to be mediated by p41/p42-MAPK activation.¹³ Karmazyn’s group⁷ reported that the inhibition of NHE activity attenuated the hypertrophy that follows myocardial infarction. Camilión de Hurtado et al¹⁴ recently reported that chronic NHE blockade in vivo . . . [Full Text of this Article]

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