Humoral control of cardiac remodeling in fish: role of Angiotensin II.

Angiotensin II (AngII), the principal effector of the Renin-Angiotensin-System (RAS), is a multipotent hormone whose biological actions include short-term modulation as well as long-term adjustments. In the eel heart, AngII elicits short-term inotropic and chronotropic effects. However, information regarding the influence of AngII on cardiac remodeling, expressed as morphological and hemodynamic changes, is lacking. To clarify the putative actions of AngII on eel cardiac remodeling, we used freshwater eels (Anguilla anguilla) intraperitoneally injected for 4 weeks with saline or AngII (0.4 or 1.2 nmol g BW(-1)) or AngII (1.2 nmol g BW(-1)) plus the AT₂ receptor antagonist CGP42112. Using an in vitro working heart preparation, the cardiac response (stroke volume changes) to preload and afterload increases has been evaluated. Hearts of all groups showed similar Frank-Starling responses. However, in response to afterload increases, stroke volume rapidly decreased in control hearts, while it was better maintained in AngII-treated counterparts. These effects were abolished by an antagonist of the AT₂ receptor, whose cardiac expression was revealed by western blotting analysis. We also found by immunolocalization and immunoblotting that AngII influences both expression and localization of molecules which regulate cell growth [such as c-kit, heat shock protein 90 (Hsp-90), endothelial Nitric Oxide Synthase "(eNOS)-like" isoform] and apoptosis [i.e. apoptosis repressor with CARD domain (ARC)], thus playing a role in cardiac long-term adjustments. These results point to a role of AngII in eel heart remodeling, providing new insights regarding the modulation of cardiac plasticity in fish.