Dept. of Biology, Ecology and Earth Sciences (B.E.ST), University of Calabria, Italy.
Gen Comp Endocrinol. 2013 Dec 1;194:189-97. doi: 10.1016/j.ygcen.2013.09.009. Epub 2013 Sep 27.
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.
血管紧张素 II（AngII）是肾素-血管紧张素系统（RAS）的主要效应物，是一种多功能激素，其生物学作用包括短期调节和长期调节。在鳗鱼心脏中，AngII 引起短期的变力和变时作用。然而，关于 AngII 对心脏重构的影响（表现为形态和血流动力学变化）的信息尚不清楚。为了阐明 AngII 对鳗鱼心脏重构的潜在作用，我们使用淡水鳗鱼（Anguilla anguilla）腹膜内注射盐水或 AngII（0.4 或 1.2 nmol g BW(-1)) 或 AngII（1.2 nmol g BW(-1)) 加 AT₂ 受体拮抗剂 CGP42112 4 周。使用离体工作心脏制备，评估了心脏对前负荷和后负荷增加的反应（每搏量变化）。所有组的心脏均表现出相似的 Frank-Starling 反应。然而，在对后负荷增加的反应中，对照组的心脏中每搏量迅速下降，而 AngII 处理组的心脏中每搏量更好地维持。这些作用被 AT₂ 受体拮抗剂所消除，Western 印迹分析显示该拮抗剂在心脏中表达。我们还通过免疫定位和免疫印迹发现，AngII 影响调节细胞生长的分子（如 c-kit、热休克蛋白 90（Hsp-90）、内皮型一氧化氮合酶（eNOS）样同工型）和细胞凋亡（即含 CARD 结构域的凋亡抑制剂（ARC）的表达和定位，从而在心脏的长期调节中发挥作用。这些结果表明 AngII 在鳗鱼心脏重构中的作用，为鱼类心脏可塑性的调节提供了新的见解。
