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Na+/H+ Exchanger and Myocardial Hypertrophy

  • Chapter
Signal Transduction and Cardiac Hypertrophy

Part of the book series: Progress in Experimental Cardiology ((PREC,volume 7))

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Summary

Na+/H+ exchanger (NHE) is hyperactive in the hypertensive hypertrophied myocardium. Regression of cardiac hypertrophy (CH) induced by prolonged antihypertensive therapy with compounds of different pharmacological profiles (angiotensin converting enzyme inhibition, slow calcium channel and angiotensin II type 1 receptor blockade) normalizes the hyperactivity of myocardial NHE. Chronic treatment with selective NHE-1 inhibitors induced the regression of CH in SHR. Considered as a whole, these data support the notion of a causal link between the hyperactivity of the NHE-1 and the development of CH.

Established Investigators of Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina.

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References

  1. Bianchini L, L’Allemain G, Pouysségur J. 1997. The p42/p44 mitogen-activated protein kinase cascade is determinant in mediating activation of the Na+/H+ exchanger (NHE1 isoform) in response to growth factors. J Biol Chem 272:271–279.

    Article  PubMed  CAS  Google Scholar 

  2. Yamazaki T, Komuro I, Yazaki Y. 1998. Signaling pathways for cardiac hypertrophy. Cell Signal 10:693–698.

    Article  PubMed  CAS  Google Scholar 

  3. Grinstein S, Rotin D, Mason M. 1989. Na+/H+ exchange and growth factor-induced cytosolic pH changes: role in cellular proliferation. Biochem Biophys Acta 988:73–97.

    Article  PubMed  CAS  Google Scholar 

  4. Counillon L, Pouysségur J. 1995. Structure-function studies and molecular regulation of the growth factor activatable sodium-hydrogen exchanger (NHE-1). Cardiov Res 29:147–154.

    CAS  Google Scholar 

  5. Takewaki S-I, Kuro-o M, Hiroi Y, Yamazaki T, Noguchi T, Miyagishi A, Nakahara K-I, Aikawa M, Manabe I, Yazaki Y, Nagai R. 1995. Activation of Na+-H+ antiporter (NHE-1) gene expression during growth, hypertrophy and proliferation of the rabbit cardiovascular system. J Mol Cell Cardiol 27:729–742.

    Article  PubMed  CAS  Google Scholar 

  6. 6. Sardet C, Fafournoux P, Pouysségur J. 1991. α-Thrombin, epidermal growth factor, and okadaic acid activate the Na+/H+ exchanger, NHE-1, by phosphorylating a set of common sites. J Biol Chem 266:19166–19171.

    PubMed  CAS  Google Scholar 

  7. Grinstein S, Woodside M, Sardet C, Pouyssegur J, Rodin D. 1992. Activation of the Na+/H+ antiporter during cell volume regulation: evidence for a phosphorylation-independent mechanism. J Biol Chem 267:23823–23828.

    PubMed  CAS  Google Scholar 

  8. Marbán E, Koretsune Y 1990. Cell calcium, oncogenes and hypertrophy. Hypertension 15:652–658.

    Article  PubMed  Google Scholar 

  9. Mende U, Kagen A, Cohen J, Aramburu J, Schoen FJ, Neer EJ. 1998. Transient cardiac expression of constitutively activated Gq leads to cardiac hypertrophy and dilated cardiomyopaty by calcineurin-dependent and independent pathways. Proc Natl Acad Sci USA 95:13893–13898.

    Article  PubMed  CAS  Google Scholar 

  10. Moor AN, Fliegel L. 1999. Protein kinase-mediated regulation of the Na+/H+ exchange in the rat myocardium by mitogen-activated protein kinase-dependent pathways. J Biol Chem 274: 22985–22992.

    Article  PubMed  CAS  Google Scholar 

  11. Snabaitis AK, Yokoyama H, Avkiran M. 2000. Roles of mitogen-activated protein kinases and protein kinase C in alpha (1A)-adrenoceptor-mediated stimulation of the sarcolemmal Na+-H+ exchanger. Circ Res 86:214–220.

    Article  PubMed  CAS  Google Scholar 

  12. Cingolani HE, Pérez NG, Camilión de Hurtado MC. Stretch-elicited autocrine/paracrine mechanism in the heart. This book.

    Google Scholar 

  13. Pérez NG, Alvarez BV, Camilión de Hurtado MC, Cingolani HE. 1995. pHi regulation in myocardium of the spontaneously hypertensive rat. Compensated enhanced activity of the Na+-H+ exchanger. Circ Res 77:1192–1200.

    Article  PubMed  Google Scholar 

  14. Schussheim AE, Radda GK. 1995. Altered Na+-H+ exchange activity in the spontaneously hypertensive perfused rat heart. J Mol Cell Cardiol 27:1475–1481.

    Article  PubMed  CAS  Google Scholar 

  15. de la Sierra A, Coca A, Paré JC, Sanitize M, Vas V, Urbano-Marquez A. 1993. Erythrocyte ion fluxes in essential hypertensive patients with left ventricular hypertrophy. Circulation 88:1628–1633.

    Article  PubMed  Google Scholar 

  16. Siczkowski M, Davies JE, Ng LL. 1994. Sodium-hydrogen antiporter protein in normotensive Wistar Kyoto and spontaneously hypertensive rats. J Hypert 12:775–781.

    Article  CAS  Google Scholar 

  17. Chiappe de Cingolani G, Morgan P, Mundina-Weilenmann C, Casey J, Fujinaga J, Camilión de Hurtado M, Cingolani H. 2001. Hyperactivity and altered mRNA isoform expression of the Cl- /HCO3 - anion exchanger in the hypertrophied myocardium. Cardiov Res 56:71–79.

    Article  Google Scholar 

  18. Ennis IL, Alvarez BV, Camilión de Hurtado MC, Cingolani HE. 1998. Enalapril induces regression of cardiac hypertrophy and normalization of pHi regulatory mechanisms. Hypertension 31:961–967.

    Article  PubMed  CAS  Google Scholar 

  19. Cingolani HE, Alvarez BV, Ennis IL, Camilión de Hurtado MC. 1998. Stretch-induced alkanization of feline papillary muscle. An autocrine-paracrine system. Circ Res 83:775–779.

    Article  PubMed  CAS  Google Scholar 

  20. Camilión de Hurtado MC, Alvarez BV, Pérez NG, Ennis IL, Cingolani HE. 1998. Angiotensin II activates Na+-independent Cl--HCO3 - exchange in ventricular myocardium. Circ Res 82:473–481.

    Article  PubMed  Google Scholar 

  21. Camilión de Hurtado MC, Alvarez BV, Ennis IL, Cingolani HE. 2000. Stimulation of myocardial Na+-independent Cl--HCO3 - exchanger by endogenous endothelin. Circ Res 86:622–626.

    Article  Google Scholar 

  22. Hoffinan G, Ko Y, Sachinidis A, Gobel BO, Vetter H, Rosskopf D, Siffert W, Dussing R. 1995. Kinetics of Na+/H+ exchange in vascular smooth muscle cells from WKY and SHR: effects of phorbol ester. Am J Physiol 268:C14–20.

    Google Scholar 

  23. Livne AA, Aharonovitz O, Paran E. 1991. Higher Na+/H+ exchange rate and more alkaline intracellular pH set-point in essential hypertension: effects of protein kinase modulation in platelets. J Hypertens 9:1013–1019.

    Article  PubMed  CAS  Google Scholar 

  24. Siczkowski M, Ng LL. 1996. Phorbol ester activation of the rat vascular myocyte Na+/H+ exchange isoform 1. Hypertension 27:859–866.

    Article  PubMed  CAS  Google Scholar 

  25. Ng LL, Sweeney FP, Siczkowski M, Davies JE, Quinn PA, Krolwewski B, Krolwewski AS. 1995. Na+/H+ antiporter phenotype, abundance, and phosphorylation of immortalized lymphoblasts from humans with hypertension. Hypertension 25:971–977.

    Article  PubMed  CAS  Google Scholar 

  26. Fortuno A, Tisaire J, Lopez R, Bueno J, Diez J. 1997. Angiotensin converting enzyme inhibition corrects Na+/H+ exchanger overactivity in essential hypertension. Am J Hypertens 10:84–93.

    Article  PubMed  CAS  Google Scholar 

  27. Sánchez RA, Gimenez MI, Migliorini M, Giannone C, Ramirez AJ, Weder AB. 1997. Erythrocyte sodium-lithium countertransport in non-modulating offspring and essential hypertensive individuals: response to enalapril. Hypertension 30:99–105.

    Article  PubMed  Google Scholar 

  28. Sadoshima J, Xu Y, Slayter HS, Izumo S. 1993. Autocrine release of angiotensin II mediates stretch-induced hypertrophy of cardiac myocytes in vitro. Cell 75:977–984.

    Article  PubMed  CAS  Google Scholar 

  29. Yamazaki T, Komuro I, Kudoh S, Zou Y, Shiojima I, Hiroi Y, Mizuno T, Maemura K, Kurihara H, Aikawa R, Takano H, Yazaki Y 1996. Endothehn-1 is involved in mechanical stress-induced cardiomyocyte hypertrophy. J Biol Chem 271:3221–3228.

    Article  PubMed  CAS  Google Scholar 

  30. Scholz W, Albus U, Counillon L, Gögelein H, Lang HJ, Linz W, Weichert A, Schölkens BA. 1995. Protective effects of HOE642, a selective sodium-hydrogen exchange subtype 1 inhibitor, on cardiac ischaemia and reperfusion. Cardiov Res 29:260–268.

    CAS  Google Scholar 

  31. Gumina RJ, Buerger E, Eickmeier C, Moore J, Daemmgen J, Gross JG. 1999. Inhibition of the Na+/H+ exchanger confers greater cardioprotection against 90 minutes of myocardial ischemia than ischemic preconditions in dogs. Circulation 100:2519–2526.

    Article  PubMed  CAS  Google Scholar 

  32. Camilión de Hurtado MC, Portiansky EL, Pérez NG, Rebolledo OR, Cingolani HE. 2002. Regression of cardiomyocyte hypertrophy in SUR following chronic inhibition of the Na+/H+ exchanger. Cardiovasc Res 53(4):862–868.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Centro de Investigaciones Cardiovasculares, Facultad de Ciencias Médicas, Universidad Nacional de La Plata, 60 y 120 (1900), La Plata, Argentina

    María C. Camilión de Hurtado, Néstor G. Pérez, Irene L. Ennis, Bernardo V. Alvarez & Horacio E. Cingolani

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  1. María C. Camilión de Hurtado
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  2. Néstor G. Pérez
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  3. Irene L. Ennis
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  4. Bernardo V. Alvarez
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  5. Horacio E. Cingolani
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Corresponding author

Correspondence to María C. Camilión de Hurtado .

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Editors and Affiliations

  1. Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre Faculty of Medicine, University of Manitoba, Winnipeg, Canada

    Naranjan S. Dhalla PhD, MD (Hon), DSc (Hon) (Distinguished Professor and Director), Larry V. Hryshko PhD (Associate Professor), Elissavet Kardami PhD (Professor) & Pawan K. Singal PhD, DSc (Professor) (Distinguished Professor and Director),  (Associate Professor),  (Professor) &  (Professor)

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© 2003 Springer Science+Business Media New York

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Camilión de Hurtado, M.C., Pérez, N.G., Ennis, I.L., Alvarez, B.V., Cingolani, H.E. (2003). Na+/H+ Exchanger and Myocardial Hypertrophy. In: Dhalla, N.S., Hryshko, L.V., Kardami, E., Singal, P.K. (eds) Signal Transduction and Cardiac Hypertrophy. Progress in Experimental Cardiology, vol 7. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-0347-7_10

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  • DOI: https://doi.org/10.1007/978-1-4615-0347-7_10

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-5032-3

  • Online ISBN: 978-1-4615-0347-7

  • eBook Packages: Springer Book Archive

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