© 1998 American Heart Association, Inc.
Editorial |
Angiotensin and Endothelin
Messengers That Couple Ventricular Stretch to the Na+/H+ Exchanger and Cardiac Hypertrophy
Correspondence to David E. Dostal, PhD, Pennsylvania State College of Medicine, Henry Hood MD Research Program, Sigfried and Janet Weis Center for Research, 100 North Academy Ave, Danville, PA 17822. E-mail ddostal@psghs.edu
Key Words: angiotensin II • endothelin-1 • Na+/H+ exchanger • mechanical stretch • myocardium
Changes in intracellular pH (pHi) can produce marked effects on cardiac function, and, therefore, it is important that the cell possess mechanisms by which pHi is regulated, especially after intracellular acidosis associated with myocardial ischemia. The Na+/H+ exchanger (NHE) and the Na+/HCO3- symport represent the 2 major pathways by which alkalinization occurs in cardiac cells. The NHE not only regulates pHi but also cell volume and intracellular signaling in response to a variety of stimuli.
Na+/H+ Exchanger and Cardiac Growth
The NHE in mammalian
myocardium1 has received considerable
attention in the past decade, because it has been linked to cardiac
growth and reperfusion injury.2 3 The NHE is
activated by mechanical stretch in cultured cardiac myocytes
and is thought to be a primary factor in influencing the anabolic state
of the ventricular myocardium in response to
pressure overload.4 5 Activation of the NHE
occurs via phosphorylation of the cytoplasmic domain,
which appears to be mediated by protein kinase
C.6 Mechanical stretch of neonatal cardiac
myocytes has also been associated with activation of second messengers,
such as inositol triphosphate, protein kinase C, Raf-1 kinase, and
mitogen-activated protein (MAP) kinase, all of which can
contribute to reexpression of a number of fetal genes associated with
cardiac hypertrophy, including ß-myosin heavy chain,
skeletal 
-actin, and atrial natriuretic
peptide.7 In studies using neonatal rat cardiac
myocytes cultured on elastic membranes, stretch-mediated increases in
MAP kinase activity and protein synthesis were attenuated by treatment
of cells with the NHE antagonist Hoe
694,2 8 suggesting that the NHE has an important
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