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长期依那普利治疗及低盐饮食对已患高血压的 Dahl 盐敏感大鼠存活率的有益影响。

Beneficial effects of long-term enalapril treatment and low-salt intake on survival rate of dahl salt-sensitive rats with established hypertension.

作者信息

Kodama K, Adachi H, Sonoda J

机构信息

Cardiovascular Research Unit, and Drug Safety Research Laboratory, Tsukuba Research Laboratories, Eisai Co., Ltd., Tsukuba, Ibaraki 300-26, Japan.

出版信息

J Pharmacol Exp Ther. 1997 Nov;283(2):625-9.

PMID:9353378
Abstract

We investigated the effects of long-term treatment with the angiotensin-converting enzyme inhibitor enalapril and low-salt intake on the survival rate of Dahl salt-sensitive rats fed a high-salt (6.0% NaCl) diet. The systolic blood pressure of the rats increased gradually from 5 weeks of age and reached >240 mm Hg at 12 weeks of age. At this point, a low-salt diet group received a placebo (group 1, n = 10), and the high-salt diet group was divided into three groups: those given a placebo with the high-salt diet (group 2, n = 15), those given a chow change from a high- to a low-salt diet with a placebo (group 3, n = 14) and those given enalapril (30 mg/kg/day p.o., group 4, n = 14). At 19 weeks of age, all rats in group 1 were alive, and the survival rate of group 2 was only 40% (P < .001 vs. group 1). The survival rates of both groups 3 and 4 were significantly better: 86% (P < .01 vs. group 2) and 93% (P < .01), respectively. This beneficial effect on mortality was accompanied by an amelioration of the elevated plasma creatinine and urea nitrogen levels and a decrease in the glomerular sclerosis lesion scores in both groups. These results suggested that a high-salt content diet and the renin-angiotensin system are deterioration factors in lethal renal damage and the limitation of the diet salt content and inhibition of the renin-angiotensin system are important to improve the survival rate in high-salt-loaded hypertensive Dahl salt-sensitive rats.

摘要

我们研究了血管紧张素转换酶抑制剂依那普利长期治疗及低盐摄入对喂食高盐(6.0%氯化钠)饮食的 Dahl 盐敏感大鼠存活率的影响。大鼠的收缩压从 5 周龄开始逐渐升高,在 12 周龄时达到>240 mmHg。此时,低盐饮食组接受安慰剂(第 1 组,n = 10),高盐饮食组分为三组:接受高盐饮食加安慰剂的组(第 2 组,n = 15)、接受从高盐饮食改为低盐饮食加安慰剂的组(第 3 组,n = 14)和接受依那普利的组(30 mg/kg/天,口服,第 4 组,n = 14)。在 19 周龄时,第 1 组的所有大鼠均存活,第 2 组的存活率仅为 40%(与第 1 组相比,P <.001)。第 3 组和第 4 组的存活率均显著更高:分别为 86%(与第 2 组相比,P <.01)和 93%(P <.01)。这种对死亡率的有益影响伴随着两组血浆肌酐和尿素氮水平升高的改善以及肾小球硬化病变评分的降低。这些结果表明,高盐饮食和肾素 - 血管紧张素系统是致死性肾损伤的恶化因素,限制饮食盐含量和抑制肾素 - 血管紧张素系统对于提高高盐负荷高血压 Dahl盐敏感大鼠的存活率很重要。

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