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Abstract

Introduction

Apoptosis and angiotensin II (Ang II) have been suggested as possible causes of arrhythmias. In addition, Ang II via Ang II type I (AT1-) receptors, has been demonstrated to induce cardiomyocyte apoptosis. The transgenic m(Ren-2)27 (TG) rat carries the additional Ren-2 gene, the expression of which results in an increase in cardiac Ang II, thus potentially affecting the cell growth/death equilibrium. In this study we have investigated the effect of Ang II, via AT1-receptors, on mediating apoptosis in a cardiac conduction system (SA node and AV nodes).

Materials and methods

Heart sections from male two-day, one-week and two-week TG and Sprague-Dawley (SD) rats were stained with Masson Trichrome to localise the SA and AV nodes. The sections containing SA or AV nodes were processed for quantitation of apoptotic nuclei and AT1-receptors.

Results

The number of apoptotic nuclei/mm² in the SA and AV nodes were found to decrease from two days to two weeks in both the TG and the SD rats, and the number of apoptotic nuclei/mm² in the TG groups was significantly higher than that of the SD groups for all ages (p<0.05). The number of AT₁-receptors/mm² in the SA node were found to decrease with increasing age, whereas the number of AT₁-receptors/mm² in the AV node was increased in both TG and SD rats and the number of AT₁-receptors/mm² in the three TG groups was significantly more than that of the three SD groups (p<0.05).

Discussion and conclusion

As a consequence of the additional renin gene in the TG rats, which results in the alteration of the local renin-angiotensin system, the numbers of AT1-receptors/mm² and apoptotic nuclei/mm² are increased. The number of apoptotic nuclei/mm² and AT1-receptors/mm² in the SA node decrease with maturation, whereas, the number of AT₁-receptors in the AV node increase. Thus, there may be a correlation between Ang II and apoptosis in the SA node, which does not appear to be present in the AV node.

Keywords

angiotensin II apoptosis conduction system AT1-receptor

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References

Myerburg RJ , Kessler KM , Castellanos A. Sudden cardiac death: epidemiology, transient risk, and intervention assessment . Ann Intern Med 1993;119:1137-97.

De Mello WC Cardiac arrhythmias: the possible role of the renin-angiotensin system . J Mol Med 2001;79:103-08.

De Mello WC , Altien P. The role of the renin-angiotensin system in the control of cell communication in the heart; effects of angiotensin II and enalapril. J Cardiovasc Pharmacol 1992;20:643-51.

De Mello WC Renin-angiotensin system and cell communication in the failing heart . Hypertension 1996;27:1267-72.

De Mello WC , Jan Danser AH Angiotensin II and the heart. On the intracrine renin angiotensin system. Hypertension 2000;35:1183-8.

De Mello WC Intracellular angiotensin II regulates the inward calcium current in cardiac myocytes. Hypertension 1998;32:976-82.

De Mello WC

Is an intracellular renin-angiotensin system involved in the control of cell communication in heart?

J Cardiovasc Pharmacol 1994;23:640-6.

James TN , Martin E. , Willis III PW , Lohr TO Apoptosis as a possible cause of gradual development of complete heart block and fatal arrhythmias associated with absence of the AV node, sinus, and internodal pathways. Circulation 1996;93: 1424-32.

Cigola E. , Kajstura LB , Meggs LG , Anversa P. Angiotensin II activates programmed myocyte cell death in vitro. Exp Cell Res 1997;231:363-71.

10.

Kajstura J. , Cigola E. , MalhotraA. et al.Angiotensin II induces apoptosis of adult ventricular myocytes in vitro. J Mol Cell Cardiol 1997;29:859-70.

11.

Lee M. , Bohm M. , Kim S. et al. Differential gene expression of renin and angiotensin in the TGR (mREN-2)27 transgenic rat. Hypertension 1995;25:570-80.

12.

Campbell DJ , Rong P. , Kladis A. , Rees B. , Ganten D. , Skinner SL Angiotensin and bradykinin peptides in the TGR (mRen-2)27 rat. Hypertension 1995;25:1014-20.

13.

James TN Normal and abnormal consequences of apoptosis in the human heart: from postnatal morphogenesis to paroxysmal arrhythmias. Circulation 1994;90:556-73.

14.

MayhewTM The new stereological methods for interpreting functional morphology from slices of cells and organs. Exp Physio 1991 ;76:639-65.

15.

Liu JJ , Peng L. , Bradley CJ , Zulli A. , Shen J. , Buxton BF Increased apoptosis in the heart of genetic hypertension, associated with increased fibroblasts. Cardiovasc Res 2000 ;45:729-35.

16.

Dosemeci RS , Dhallan RS , Cohen NM , Lederer WJ , Roger TB Phorbol ester increase clacium current and stimulates the effects of angiotensin II on cultured neonatal rat heart myocytes . Circ Res 1988;62:347-57.

17.

Peitsch MC , Polzas B. , Stephan H. et al. Characterization of the endogenous deoxyribonuclease involved in nuclear DNA degradation during apoptosis (programmed cell death). EMBO J 1993;12: 371-7.

18.

Izumiya Y. , Kim S. , Izumi Y. et al.Apoptosis signal-regulating kinase 1 plays a pivotal role in angiotensin II-induced cardiac hypertrophy and remodeling. Circ Res 2003;93:874-83.

19.

Grishko V. , Pastukh V. , Solodushko V. , Gillespie M. , Azuma J. , Schaffer S. Apoptotic cascade initiated by angiotensin II in neonatal cardiomyocytes: role of DNA damage. Am J Physiol Heart Circ Physiol 2003;285:H2364-H2372.

20.

Kajstura J. , Mansukhani M. , Cheng W. et al. Programmed cell death and expression of the protooncogene bcl-2 in myocytes during postnatal maturation of the heart. Exp Cel Res 1995; 219:110-21.

21.

Kass RS , Blair ML Effects of angiotensin II on membrane current in cardiac Purkinje fibers. J Mol Cell Cardiol 1981;13: 797-809.

22.

Sechi LA , Griffin CA , Grady EF , Kalinyak JE , Schambelan M. Characterization of angiotensin II receptor subtypes in rat heart . Circ Res 1992;71:1482-9.

Angiotensin II may mediate apoptosis via AT1-receptors in the rat cardiac conduction system

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