Lacolley Patrick, Labat Carlos, Pujol Alex, Delcayre Claude, Benetos Athanase, Safar Michel
INSERM EMI U0107, Paris, France.
Circulation. 2002 Nov 26;106(22):2848-53. doi: 10.1161/01.cir.0000039328.33137.6c.
Previous studies have demonstrated the development of cardiac fibrosis in aldosterone (Aldo)-salt hypertensive rats. Our aim was to determine the effects of Aldo and the Aldo receptor antagonist eplerenone (Epl) on in vivo mechanical properties of the carotid artery using echo-tracking system.
Aldo was administered (1 microg/h) in uninephrectomized Sprague-Dawley rats (SD) receiving a high-salt diet from 8 to 12 weeks of age. Uninephrectomized control SD rats received a normal salt diet without Aldo. Three groups of Aldo-salt rats were treated with 1, 10, or 30 mg/kg(-1) x d(-1) of Epl by gavage. Elasticity was measured by elastic modulus (Einc)-wall stress curves using medial cross-sectional area (MCSA). The structure of the arterial wall was analyzed by histomorphometry (elastin and collagen), immunohistochemistry (EIIIA fibronectin, Fn), and Northern blot (collagens I and III). Aldo produced increased systolic arterial pressure, pulse pressure, Einc, MCSA, and EIIIA Fn with no change in wall stress or elastin and collagen densities compared with controls without Aldo. No differences in collagen mRNA levels were detected between groups. Epl blunted the increase in pulse pressure in Aldo rats and normalized Einc-wall stress curves, MCSA, and EIIIA Fn. These effects were dose dependent and not accompanied by a reduction in wall stress.
Aldo is able to increase arterial stiffness associated with Fn accumulation, independently of wall stress. The preventive effects of Epl suggest a direct role for mineralocorticoid receptors in mechanical and structural alterations of large vessels in rat hyperaldosteronism.
先前的研究已证实醛固酮(Aldo)-盐性高血压大鼠会出现心脏纤维化。我们的目的是使用回声跟踪系统来确定醛固酮和醛固酮受体拮抗剂依普利酮(Epl)对颈动脉体内力学性能的影响。
对8至12周龄接受高盐饮食的单侧肾切除Sprague-Dawley大鼠(SD)给予醛固酮(1微克/小时)。单侧肾切除的对照SD大鼠接受不含醛固酮的正常盐饮食。三组醛固酮-盐大鼠通过灌胃给予1、10或30毫克/千克-1×天-1的依普利酮。使用中膜横截面积(MCSA)通过弹性模量(Einc)-壁应力曲线测量弹性。通过组织形态计量学(弹性蛋白和胶原蛋白)、免疫组织化学(EIIIA纤连蛋白,Fn)和Northern印迹(胶原蛋白I和III)分析动脉壁结构。与未给予醛固酮的对照组相比,醛固酮使收缩期动脉压、脉压、Einc、MCSA和EIIIA Fn升高,而壁应力或弹性蛋白和胶原蛋白密度无变化。各组之间未检测到胶原蛋白mRNA水平的差异。依普利酮减弱了醛固酮大鼠脉压的升高,并使Einc-壁应力曲线、MCSA和EIIIA Fn恢复正常。这些作用呈剂量依赖性,且不伴有壁应力的降低。
醛固酮能够增加与Fn积聚相关的动脉僵硬度,与壁应力无关。依普利酮的预防作用表明盐皮质激素受体在大鼠醛固酮增多症大血管的力学和结构改变中起直接作用。