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瑞舒伐他汀可减轻去氧皮质酮盐诱导的高血压大鼠的高血压所致心血管重塑,而不影响其血压。

Rosuvastatin attenuates hypertension-induced cardiovascular remodeling without affecting blood pressure in DOCA-salt hypertensive rats.

作者信息

Loch David, Levick Scott, Hoey Andrew, Brown Lindsay

机构信息

Department of Physiology and Pharmacology, School of Biomedical Sciences, The University of Queensland, Australia.

出版信息

J Cardiovasc Pharmacol. 2006 Mar;47(3):396-404. doi: 10.1097/01.fjc.0000210072.48991.f6.

Abstract

The pleiotropic effects of statins represent potential mechanisms for the treatment of end-organ damage in hypertension. This study has investigated the effects of rosuvastatin in a model of cardiovascular remodeling, the DOCA-salt hypertensive rat. Male Wistar rats weighing 300 to 330 g were uninephrectomized (UNX) or UNX and treated with DOCA (25 mg subcutaneously every fourth day) and 1% NaCl in the drinking water. Compared with UNX controls, DOCA-salt rats developed hypertension, cardiovascular hypertrophy, inflammation with perivascular and interstitial cardiac fibrosis, endothelial dysfunction, and prolongation of ventricular action potential duration at 28 days. Rosuvastatin-treated rats received 20 mg/kg/d of the drug in 10% Tween 20 by oral gavage for 32 days commencing 4 days before uninephrectomy. UNX and DOCA-salt controls received vehicle only. Rosuvastatin therapy attenuated the development of cardiovascular hypertrophy, inflammation, fibrosis, and ventricular action potential prolongation, but did not modify hypertension or vascular dysfunction. We conclude that the pleiotropic effects of rosuvastatin include attenuation of aspects of cardiovascular remodeling in the DOCA-salt model of hypertension in rats without altering systolic blood pressure.

摘要

他汀类药物的多效性作用代表了治疗高血压终末器官损伤的潜在机制。本研究调查了瑞舒伐他汀在心血管重塑模型(去氧皮质酮盐高血压大鼠)中的作用。体重300至330克的雄性Wistar大鼠进行单侧肾切除(UNX),或先进行UNX,然后每四天皮下注射去氧皮质酮(25毫克),并饮用含1%氯化钠的水。与UNX对照组相比,去氧皮质酮盐大鼠在28天时出现高血压、心血管肥大、伴有血管周围和间质心脏纤维化的炎症、内皮功能障碍以及心室动作电位时程延长。瑞舒伐他汀治疗组大鼠在单侧肾切除前4天开始,通过口服灌胃给予20毫克/千克/天的药物(溶于10%吐温20),持续32天。UNX组和去氧皮质酮盐对照组仅给予赋形剂。瑞舒伐他汀治疗减轻了心血管肥大、炎症、纤维化和心室动作电位延长的发展,但未改变高血压或血管功能障碍。我们得出结论,瑞舒伐他汀的多效性作用包括在不改变收缩压的情况下减轻大鼠去氧皮质酮盐高血压模型中心血管重塑的各个方面。

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