Differences between cardiac and arterial fibrosis and stiffness in aldosterone-salt rats: Effect of eplerenone
Differences between cardiac and arterial fibrosis and stiffness in aldosterone-salt rats: Effect of eplerenone
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DOI：
10.3317/jraas.2006.004
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发表时间：
2006-03-01
影响因子：
2.9
通讯作者：
Lacolley, Patrick
中科院分区：
文献类型：
--
作者：
Nehme, Jobnny;Mercier, Nathalie;Lacolley, Patrick
背景资料。先前的实验已经分别研究了醛固酮(ALDO)-盐性高血压大鼠心脏或主动脉纤维化和僵硬的发展。我们的目的是在体内测定Aldo和Aldo受体拮抗剂依普利酮(EPL)对心脏和动脉结构和功能同步变化的影响及其相互作用。方法和结果。在8至12周龄接受高盐饮食的单肾切除的Spraogue-Dawley大鼠中，给药了Aldo。3组Aldo盐大鼠分别给予1~100 mg/kg(-1)灌胃。D(-1)EPL灌胃。动脉弹性由内侧横截面积(MCSA)的弹性系数(EINC)-壁应力曲线测量。通过组织形态计量学(弹性蛋白和胶原)、免疫组织化学(EIIIA纤维连接蛋白，FN)和Northern印迹(I型和III型胶原蛋白)对心脏和动脉壁进行分析。ALDO导致收缩压(SBP)、颈动脉EINC、MCSA和EIIIA FN升高，而壁应力、弹性蛋白和胶原密度没有变化。组间胶原基因表达水平差异无统计学意义。在同一时期，心肌质量和心肌组织中胶原mRNA和蛋白的水平显著增加。EPI使Aldo大鼠心肌胶原蛋白、管壁应力曲线、MCSA和EIIIA FN正常化。这些剂量依赖效应并不伴随着SBP和心脏肿块的持续下降。在外源性高醛固酮增多症大鼠中，Aldo独立地引起心肌胶原蛋白和动脉FN积聚，后者导致颈动脉内僵硬增加。EPI可预防心脏和动脉效应，但不能持续降低SBP。
Background. Previous experiments have studied separately the development of either cardiac or aortic fibrosis and stiffness in aldosterone (Aldo)-salt hypertensive rats. Our aim was to determine in vivo the effects of Aldo and the Aldo receptor antagonist eplerenone (Epl) on Simultaneous changes in cardiac and arterial structure and function and their interactions.Methods and Results. Aldo was administered in uninephrectomised Sprague-Dawley rats receiving a high-salt diet from 8 to 12 weeks of age. Three groups of Aldo-salt rats were treated with 1 to 100 mg/kg(-1). d(-1) Epl by gavage. Arterial elasticity was measured by elastic modulus (Einc)-wall stress curves using medial cross-sectional area (MCSA). The cardiac and arterial walls were analysed by histomorphometry (elastin and collagen), immunohistochemistry (EIIIA fibronectin, Fn), and Northern blot (collagens I and III). Aldo caused increased systolic blood pressure (SBP), carotid Einc, MCSA, and EIIIA Fn with no change in wall stress or elastin and collagen densities. No difference in collagen mRNA levels was detected between groups. During the same period, cardiac mass and collagen mRNA and protein levels increased markedly in the myocardial tissue. EpI normalised collagen in the myocardium, Einc-wall stress curves, MCSA, and EIIIA Fn in Aldo rats. These dose-dependent effects were not accompanied by a consistent reduction in SBP and cardiac mass.Conclusions. In exogenous hyperaldosteronism in the rat, Aldo causes independently myocardial collagen and arterial Fn accumulation, the latter being responsible for increased intrinsic carotid stiffness. EpI prevents both cardiac and arterial effects but does not reduce consistently SBP.