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


OBJECTIVE
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.


CONCLUSIONS
Our data suggest that local cardiac aldosterone actions contribute to the development of left ventricular interstitial fibrosis.
Minnaard-Huiban
Monica
M
Department of Pharmacology and Toxicology, Cardiovascular Research Institute, Maastricht University, Netherlands.
Hermans
J J Rob
JJ
Essen
Helma van
Hv
Bitsch
Nicole
N
Smits
Jos F M
JF
D000450:Aldosterone / Q000008:administration & dosage / Q000009:adverse effects*; D000818:Animals; D004195:Disease Models, Animal; D005355:Fibrosis / Q000139:chemically induced* / Q000503:physiopathology; D006352:Heart Ventricles / Q000187:drug effects* / Q000473:pathology; D007262:Infusions, Intravenous; D007263:Infusions, Parenteral; D008297:Male; D010496:Pericardium / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D012307:Risk Factors; D018487:Ventricular Dysfunction, Left / Q000139:chemically induced* / Q000503:physiopathology
D000450:Aldosterone