| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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 cicme{at}isis.unlp.edu.ar
Abstract—Intracellular pH is under
strict control in myocardium; H+ are extruded
from the cells by sodium-dependent mechanisms, mainly
Na+/H+ exchanger and
Na+/HCO3- symport, whereas
Na+-independent
Cl-/HCO3- exchanger extrudes
bases on intracellular alkalinization. Hypertrophic
myocardium from spontaneously hypertensive rats (SHR)
exhibits increased Na+/H+ exchange activity
that is accompanied by enhanced extrusion of bases through
Na+-independent
Cl-/HCO3- exchange. The
present experiments were designed to investigate the effect of
enalapril-induced regression of cardiac hypertrophy on the
activity of these exchangers. Male SHR and normotensive Wistar-Kyoto
rats (WKY) received enalapril maleate (20 mg/kg per day) in the
drinking water for 5 weeks. Gender- and age-matched SHR and WKY were
used as untreated controls. Enalapril treatment significantly reduced
systolic blood pressure in SHR and completely regressed cardiac
hypertrophy. Na+/H+ activity was
estimated in terms of both steady pHi value in HEPES buffer
and the rate of pHi recovery from CO2-induced
acid load. Na+-independent
Cl-/HCO3- activity was assessed
by measuring the rate of pHi recovery from intracellular
alkalinization produced by trimethylamine exposure. Regression of
cardiac hypertrophy was accompanied by normalization of
Na+/H+ and Na+-independent
Cl-/HCO3- exchange activities.
Inhibition of protein kinase C (PKC) activity with chelerythrine
(10 mmol/L) or calphostin C (50 nmol/L) returned both exchange
activities to normal values. These results show that
angiotensin-converting enzyme inhibition normalizes the
enhanced activity of both exchangers while regressing cardiac
hypertrophy. Because normalization of exchange activities
could be also achieved by PKC inhibition, the data would suggest that
PKC-dependent mechanisms play a significant role in the increased ion
exchange activities of hypertrophic myocardium and in their
normalization by angiotensin-converting enzyme
inhibition.
© 1998 American Heart Association, Inc.
Scientific Contributions
Enalapril Induces Regression of Cardiac Hypertrophy and Normalization of pHi Regulatory Mechanisms
Key Words: ion transport • hypertrophy, cardiac • angiotensin-converting enzyme inhibitors • protein kinase C • intracellular pH
This article has been cited by other articles:
 |
|
 |
|
  J. R. Casey, W. S. Sly, G. N. Shah, and B. V. Alvarez Bicarbonate homeostasis in excitable tissues: role of AE3 Cl-/HCOFormula exchanger and carbonic anhydrase XIV interaction Am J Physiol Cell Physiol, November 1, 2009; 297(5): 1091 - 1102. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. D. Garciarena, C. I. Caldiz, E. L. Portiansky, G. E. Chiappe de Cingolani, and I. L. Ennis Chronic NHE-1 blockade induces an antiapoptotic effect in the hypertrophied heart J Appl Physiol, April 1, 2009; 106(4): 1325 - 1331. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Darmellah, C. Rucker-Martin, and D. Feuvray ERM proteins mediate the effects of Na+/H+ exchanger (NHE1) activation in cardiac myocytes Cardiovasc Res, February 1, 2009; 81(2): 294 - 300. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Prasad, I. Bodi, J. W. Meyer, Y. Wang, M. Ashraf, S. J. Engle, T. Doetschman, K. Sisco, M. L. Nieman, M. L. Miller, et al. Impaired Cardiac Contractility in Mice Lacking Both the AE3 Formula Exchanger and the NKCC1 Na+-K+-2Cl- Cotransporter: EFFECTS ON Ca2+ HANDLING AND PROTEIN PHOSPHATASES J. Biol. Chem., November 14, 2008; 283(46): 31303 - 31314. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. E. Cingolani and I. L. Ennis Sodium-Hydrogen Exchanger, Cardiac Overload, and Myocardial Hypertrophy Circulation, March 6, 2007; 115(9): 1090 - 1100. [Full Text] [PDF]
|
|
|
|
 |
|
 B. V Alvarez, D. M Kieller, A. L Quon, D. Markovich, and J. R Casey Slc26a6: a cardiac chloride-hydroxyl exchanger and predominant chloride-bicarbonate exchanger of the mouse heart J. Physiol., December 15, 2004; 561(3): 721 - 734. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. L. Ennis, E. M. Escudero, G. M. Console, G. Camihort, C. G. Dumm, R. W. Seidler, M. C. Camilion de Hurtado, and H. E. Cingolani Regression of Isoproterenol-Induced Cardiac Hypertrophy by Na+/H+ Exchanger Inhibition Hypertension, June 1, 2003; 41(6): 1324 - 1329. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. E. Cingolani and M. C. Camilion de Hurtado Na+-H+ Exchanger Inhibition: A New Antihypertrophic Tool Circ. Res., April 19, 2002; 90(7): 751 - 753. [Full Text] [PDF]
|
|
|
|
|
|
S. Engelhardt, L. Hein, U. Keller, K. Klambt, and M. J. Lohse Inhibition of Na+-H+ Exchange Prevents Hypertrophy, Fibrosis, and Heart Failure in {beta}1-Adrenergic Receptor Transgenic Mice Circ. Res., April 19, 2002; 90(7): 814 - 819. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. C. Camilion de Hurtado, E. L. Portiansky, N. G. Perez, O. R. Rebolledo, and H. E. Cingolani Regression of cardiomyocyte hypertrophy in SHR following chronic inhibition of the Na+/H+ exchanger Cardiovasc Res, March 1, 2002; 53(4): 862 - 868. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Chiappe de Cingolani, P. Morgan, C. Mundina-Weilenmann, J. Casey, J. Fujinaga, M. Camilion de Hurtado, and H. Cingolani Hyperactivity and altered mRNA isoform expression of the Cl-/HCO3- anion-exchanger in the hypertrophied myocardium Cardiovasc Res, July 1, 2001; 51(1): 71 - 79. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Sandmann, M. Yu, E. Kaschina, A. Blume, E. Bouzinova, C. Aalkjaer, and T. Unger Differential effects of angiotensin AT1 and AT2 receptors on the expression, translation and function of the Na+-H+ exchanger and Na+-HCO3- symporter in the rat heart after myocardial infarction J. Am. Coll. Cardiol., June 15, 2001; 37(8): 2154 - 2165. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. M. Touyz and E. L. Schiffrin Signal Transduction Mechanisms Mediating the Physiological and Pathophysiological Actions of Angiotensin II in Vascular Smooth Muscle Cells Pharmacol. Rev., December 1, 2000; 52(4): 639 - 672. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. P. Goel, A. Vecchini, V. Panagia, and G. N. Pierce Altered cardiac Na+/H+ exchange in phospholipase D-treated sarcolemmal vesicles Am J Physiol Heart Circ Physiol, September 1, 2000; 279(3): H1179 - H1184. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Tamura, S. Said, J. Harris, W. Lu, and A. M. Gerdes Reverse Remodeling of Cardiac Myocyte Hypertrophy in Hypertension and Failure by Targeting of the Renin-Angiotensin System Circulation, July 11, 2000; 102(2): 253 - 259. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Yoshida and M. Karmazyn Na+/H+ exchange inhibition attenuates hypertrophy and heart failure in 1-wk postinfarction rat myocardium Am J Physiol Heart Circ Physiol, January 1, 2000; 278(1): H300 - H304. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P.A. van Zwieten The influence of antihypertensive drug treatment on the prevention and regression of left ventricular hypertrophy Cardiovasc Res, January 1, 2000; 45(1): 82 - 91. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. E. Cingolani Na+/H+ exchange hyperactivity and myocardial hypertrophy: Are they linked phenomena? Cardiovasc Res, December 1, 1999; 44(3): 462 - 467. [Full Text] [PDF]
|
|
|
|
|
|
B. V. Alvarez, J. Fujinaga, and J. R. Casey Molecular Basis for Angiotensin II-Induced Increase of Chloride/Bicarbonate Exchange in the Myocardium Circ. Res., December 7, 2001; 89(12): 1246 - 1253. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Engelhardt, L. Hein, U. Keller, K. Klambt, and M. J. Lohse Inhibition of Na+-H+ Exchange Prevents Hypertrophy, Fibrosis, and Heart Failure in {beta}1-Adrenergic Receptor Transgenic Mice Circ. Res., April 19, 2002; 90(7): 814 - 819. [Abstract] [Full Text] [PDF]
|
|