Effects of eprosartan on renal function and cardiac hypertrophy in rats with experimental heart failure
Effects of eprosartan on renal function and cardiac hypertrophy in rats with experimental heart failure
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DOI：
10.1161/01.hyp.32.4.746
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发表时间：
1998-10-01
期刊：
影响因子：
8.3
通讯作者：
Winaver, J
中科院分区：
文献类型：
--
作者：
Brodsky, S;Gurbanov, K;Winaver, J
肾素-血管紧张素系统的激活可能导致充血性心力衰竭时肾和心功能的紊乱。本研究观察了选择性血管紧张素II受体拮抗剂依普沙坦对充血性心力衰竭大鼠肾血流动力学和排泄参数的影响以及对心脏肥厚形成的影响。静脉注射依普沙坦(1.0 mg/kg)后，大鼠肾血流量显著增加(+34%)，计算的肾血管阻力持续下降(-33%)。这些对肾脏血流动力学的影响比在假手术对照组大鼠中观察到的更明显，并且在平均动脉压显著下降(-12%)的情况下发生。此外，依普沙坦可优先增加充血性心力衰竭大鼠肾皮质血液灌注量，并显著增加肾小球滤过率。与未治疗的心力衰竭大鼠相比，慢性给予依普沙坦(每天5.0 mg/kg，连续7d，经腹膜腔内植入渗透性微泵)可显著增加尿钠排泄量。此外，对于充血性心力衰竭的盐保留大鼠，给予依普沙坦后，尿钠排泄逐渐增加，并最终恢复。最后，早期使用依普沙坦比血管紧张素转换酶抑制剂依那普利在更大程度上阻止了动静脉瘘大鼠心肌肥厚的发展。这些发现强调了血管紧张素II在介导心力衰竭时肾功能损害和诱导心脏肥厚中的重要性，并进一步表明血管紧张素II受体拮抗剂可能是治疗严重心力衰竭这些后果的有效方法。
Activation of the renin-angiotensin system may contribute to the derangement in renal and cardiac function in congestive heart failure. The present study evaluated the effects of eprosartan, a selective angiotensin II receptor antagonist, on renal hemodynamic and excretory parameters and on the development of cardiac hypertrophy in rats with aortocaval fistula, an experimental model of congestive heart failure. Infusion of eprosartan (1.0 mg/kg) in rats with aortocaval fistula produced a significant increase (+34%) in total renal blood flow and a sustained decrease (-33%) in the calculated renal vascular resistance. These effects on renal hemodynamics were more pronounced than those observed in sham-operated control rats and occurred despite a significant fall (-12%) in mean arterial blood pressure. Moreover, eprosartan caused a preferential increase in renal cortical blood perfusion and significantly increased glomerular filtration in rats with congestive heart failure. Chronic administration of eprosartan (5.0 mg/kg per day for 7 days through osmotic minipumps inserted intraperitoneally on the day of operation) resulted in a significant enhancement of urinary sodium excretion compared with nontreated rats with heart failure. Moreover, administration of eprosartan to salt-retaining rats with congestive heart failure resulted in a progressive increase and ultimate recovery in urinary sodium excretion. Finally, early treatment with eprosartan blocked the development of cardiac hypertrophy in rats with aortocaval fistula to a larger extent than the angiotensin-converting enzyme inhibitor enalapril. These findings emphasize the importance of angiotensin II in mediating the impairment in renal function and induction of cardiac hypertrophy in heart failure and further suggest that angiotensin II receptor blockade may be a useful treatment of these consequences in severe cardiac failure.