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European Journal of Heart Failure 2008 10(12):1166-1171; doi:10.1016/j.ejheart.2008.09.012
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© 2008 European Society of Cardiology

Comparison of the effects of intrapericardial and intravenous aldosterone infusions on left ventricular fibrosis in rats

Monica Minnaard-Huiban, J.J. Rob Hermans*, Helma van Essen, Nicole Bitsch and Jos F.M. Smits

Department of Pharmacology and Toxicology, Cardiovascular Research Institute, Maastricht University Netherlands

* Corresponding author. Department of Pharmacology and Toxicology, Cardiovascular Research Institute, Maastricht University, PO Box 616, 6200 MD Maastricht, The Netherlands. Tel.: +31 433881417; fax: +31 433884149. E-mail address: r.hermans{at}farmaco.unimaas.nl (J.J.R. Hermans).


  Abstract

Background: Aldosterone plays a detrimental role in the pathology of chronic heart failure. An important mechanism resides in its ability to evoke extensive fibrosis in the heart. However, the locations of the aldosterone interaction sites responsible for triggering cardiac fibrosis are puzzling. Extra-cardiac aldosterone actions are known to contribute to cardiac fibrosis but whether local cardiac aldosterone actions are involved is unclear.

Aims: This study aimed to investigate whether local aldosterone actions contribute to cardiac fibrosis in vivo.

Methods: Saline treated male Wistar rats were intravenously (systemically) or intrapericardially (locally) infused for 8 weeks with 75 or 750 ng/h aldosterone to monitor end point left ventricular epicardial collagen levels (histology).

Results: Perivascular fibrosis was observed only at high dose aldosterone infusions and was not different for the administration routes. Regarding interstitial fibrosis however, clear differences between the administration routes were seen. Intrapericardial aldosterone infusions increased interstitial collagen levels 1.72x (P<0.05) at low dose, but –surprisingly– had no significant effect at high dose. In contrast, intravenous aldosterone had no significant effect at low dose but increased interstitial collagen 1.72x (P<0.05) at high dose.

Conclusion: Our data suggest that local cardiac aldosterone actions contribute to the development of left ventricular interstitial fibrosis.

Key Words: Aldosterone • Cardiac fibrosis • Heart failure • Intrapericardial application

Received April 25, 2008; Revised August 1, 2008; Accepted September 22, 2008


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