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阿替洛尔对自发性高血压大鼠心肌细胞及亚细胞肥大的β肾上腺素能受体阻滞作用

The effects of beta adrenoceptor blockade with atenolol on myocardial cellular and subcellular hypertrophy in spontaneously hypertensive rats.

作者信息

Lauva I K, Tomanek R J

出版信息

Anat Rec. 1983 Dec;207(4):615-22. doi: 10.1002/ar.1092070409.

Abstract

In this study we investigated the effects of chronic beta adrenoreceptor blockade with atenolol on cellular and subcellular hypertrophy in spontaneously hypertensive rats (SHR). Atenolol was injected subcutaneously (20 mg/kg) twice daily commencing in four-week-old rats. The treated animals (SHR-A) were compared to their nontreated controls and normotensive, Wistar-Kyoto (WKY) controls at the age of 16 weeks. A group of atenolol-treated WKY was also studied. Chronic drug treatment was effective in attenuating the rise in systolic blood pressure characteristic of SHR, but did not normalize the values to those of WKY. Cardiac hypertrophy, characteristic of SHR, was modified by drug treatment as evidenced by left ventricular weights as well as myocardial cell size. The cells from the subendocardium underwent selective hypertrophy in SHR which was attenuated by about 50% after atenolol treatment. Stereological analysis of electron micrographs showed that while relative mitochondrial volume was not affected by treatment, relative myofibrillar volume (%) decreased in both subepicardium (SHR = 63.28 +/- 1.25; SHR-A = 56.72 +/- 1.37) and subendocardium (SHR = 66.53 +/- 1.27; SHR-A = 58.30 +/- 1.51). This change raised the mitochondrial/myofibrillar volume ratio, which is characteristically low in SHR compared to WKY. Sarcoplasm, which included all cell constituents except mitochondria, increased with atenolol treatment, but water concentration remained unchanged. The data suggest that attenuation of hypertrophy in SHR after beta blockade is associated with selective effects on the myocardial cell involving primarily the myofibrillar cell compartment.

摘要

在本研究中,我们调查了用阿替洛尔进行慢性β肾上腺素能受体阻滞对自发性高血压大鼠(SHR)细胞和亚细胞肥大的影响。从4周龄大鼠开始,每天皮下注射阿替洛尔(20mg/kg)两次。在16周龄时,将治疗组动物(SHR-A)与其未治疗的对照组以及正常血压的Wistar-Kyoto(WKY)对照组进行比较。还研究了一组用阿替洛尔治疗的WKY大鼠。慢性药物治疗有效地减轻了SHR特有的收缩压升高,但并未使其值恢复到WKY大鼠的水平。SHR特有的心脏肥大通过药物治疗得到改善,左心室重量以及心肌细胞大小证明了这一点。SHR的心内膜下层细胞发生选择性肥大,阿替洛尔治疗后这种肥大减轻了约50%。电子显微镜照片的体视学分析表明,虽然治疗对相对线粒体体积没有影响,但心外膜下层(SHR = 63.28 +/- 1.25;SHR-A = 56.72 +/- 1.37)和心内膜下层(SHR = 66.53 +/- 1.27;SHR-A = 58.30 +/- 1.51)的相对肌原纤维体积(%)均下降。这种变化提高了线粒体/肌原纤维体积比,与WKY相比,SHR的该比值通常较低。除线粒体外包含所有细胞成分的肌浆随着阿替洛尔治疗而增加,但水浓度保持不变。数据表明,β受体阻滞后SHR肥大的减轻与对心肌细胞的选择性作用有关,主要涉及肌原纤维细胞区室。

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