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

Department of Anatomy, Faculty of Science, Prince of Songkla University, Hat-Yai 90112, Thailand, uraporn.v{at}psu.ac.th

Surapong Vongvatcharanon

Department of Oral Surgery, Faculty of Dentistry, Prince of Songkla University, Hat-Yai 90112, Thailand

Nisaudah Radenahmad

Department of Anatomy, Faculty of Science, Prince of Songkla University, Hat-Yai 90112, Thailand

Pornpimol Kirirat

Department of Anatomy, Faculty of Science, Prince of Songkla University, Hat-Yai 90112, Thailand

Pranom Intasaro

Department of Anatomy, Faculty of Science, Prince of Songkla University, Hat-Yai 90112, Thailand

Prasert Sobhon

Department of Anatomy, Faculty of Science, Mahidol University, Bangkok 10400, Thailand

Terry Parker

School of Biomedical Sciences, Nottingham University, Nottingham, NG7 2UH, UK

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/mm ² 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/mm ² 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.

Key Words: angiotensin II • apoptosis • conduction system • AT1-receptor

Journal of Renin-Angiotensin-Aldosterone System, Vol. 5, No. 3, 135-140 (2004)
DOI: 10.3317/jraas.2004.030


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