Cosenzi A, Sacerdote A, Seculin P, Odoni G, Plazzotta N, Bernobich E, Bellini G
Istituto di Medicina Clinica, University of Trieste, Italy.
J Cardiovasc Pharmacol. 1999 Mar;33(3):485-91. doi: 10.1097/00005344-199903000-00020.
Normotensive rats fed a high-fructose diet (HFD) develop hypertriglyceridemia, hyperinsulinemia, and hypertension. The glomerular changes observed in the kidneys of these animals are similar to those observed in diabetic rats. The aim of this study was to evaluate whether lacidipine, a calcium antagonist, could have a protective effect with this animal model. Forty male Wistar-Kyoto (WKY) rats were divided into four groups treated with HFD + placebo; HFD + lacidipine, 0.3 mg/kg/day; HFD + lacidipine, 3 mg/kg/day; or standard diet + placebo for 4 weeks. Urinary excretion of the stable metabolic products of nitric oxide (NO) was determined, because this vasoactive agent has been found to cause hemodynamic changes in the diabetic kidney. Glomerular size was determined by means of morphometric analysis. The results of this study show that lacidipine prevents (a) the HFD-induced increase in blood pressure in a dose-dependent manner; (b) the HFD-induced increase in glomerular size and fibronectin synthesis; and (c) the increase of collagen III synthesis in the heart. The drug had no effect on the increased urinary excretion of the stable metabolic products of NO. These data suggest that lacidipine might be useful in preventing the renal and cardiac damage caused by hypertension and non-insulin-dependent diabetes mellitus.
喂食高果糖饮食(HFD)的正常血压大鼠会出现高甘油三酯血症、高胰岛素血症和高血压。在这些动物肾脏中观察到的肾小球变化与糖尿病大鼠中观察到的相似。本研究的目的是评估钙拮抗剂拉西地平对该动物模型是否具有保护作用。40只雄性Wistar-Kyoto(WKY)大鼠被分为四组,分别接受HFD + 安慰剂;HFD + 拉西地平,0.3毫克/千克/天;HFD + 拉西地平,3毫克/千克/天;或标准饮食 + 安慰剂治疗4周。测定了一氧化氮(NO)稳定代谢产物的尿排泄量,因为已发现这种血管活性物质会导致糖尿病肾脏的血流动力学变化。通过形态计量分析确定肾小球大小。本研究结果表明,拉西地平可(a)以剂量依赖的方式预防HFD诱导的血压升高;(b)预防HFD诱导的肾小球大小增加和纤连蛋白合成增加;以及(c)预防心脏中III型胶原合成增加。该药物对NO稳定代谢产物尿排泄增加没有影响。这些数据表明,拉西地平可能有助于预防高血压和非胰岛素依赖型糖尿病引起的肾脏和心脏损伤。