School of Pharmaceutical Sciences, Universiti Sains Malaysia, Minden 11800 Penang, Malaysia,
J Physiol Biochem. 2012 Sep;68(3):353-63. doi: 10.1007/s13105-012-0147-1. Epub 2012 Jan 27.
The aim of this study is to assess the effects of losartan and carvedilol on metabolic parameters and renal haemodynamic responses to angiotensin II (Ang II) and adrenergic agonists in the model of fructose-fed rat. Thirty-six Sprague-Dawley rats were fed for 8 weeks either 20% fructose solution (F) or tap water (C) ad libitum. F or C group received either losartan or carvedilol (10 mg/kg p.o.) daily for the last 3 weeks of the study (FL and L) and (FCV and CV), respectively, then in acute studies the renal vasoconstrictor actions of Ang II, noradrenaline (NA), phenylephrine (PE) and methoxamine (ME) were determined. Data, mean±SEM were analysed using ANOVA with significance at P <0.05. Losartan and carvedilol decreased the area under the glucose tolerance curve of the fructose-fed group. The responses (%) to NA, PE, ME and Ang II in F were lower (P <0.05) than C (F vs. C, 17±2 vs. 38±3; 24±2 vs. 48±2; 12±2 vs. 34±2; 17±2 vs. 26±2), respectively. L had higher (P <0.05) responses to NA and PE while CV had blunted (P <0.05) responses to NA, PE and Ang II compared to C (L, CV vs. C, 47±3, 9±2 vs. 38±3; 61±3, 29±3 vs. 48±2; 16±3, 4±3 vs. 26±2), respectively. FL but not FCV group had enhanced (P <0.05) responses to NA, PE and ME compared to F (FL vs. F, 33±3 vs. 17±2; 45±3 vs. 24±2; 26±3 vs. 12±2), respectively. Losartan and carvedilol had an important ameliorating effect on fructose-induced insulin resistance. Losartan treatment could be an effective tool to restore normal vascular reactivity in the renal circulation of the fructose-fed rat.
本研究旨在评估氯沙坦和卡维地洛对果糖喂养大鼠模型中血管紧张素 II (Ang II) 和肾上腺素能激动剂代谢参数和肾血流动力学反应的影响。36 只 Sprague-Dawley 大鼠自由饮用 20%果糖溶液 (F) 或自来水 (C) 8 周。F 或 C 组在研究的最后 3 周每天分别给予氯沙坦或卡维地洛 (10 mg/kg po) (FL 和 L) 和 (FCV 和 CV),然后在急性研究中确定 Ang II、去甲肾上腺素 (NA)、苯肾上腺素 (PE) 和间羟胺 (ME) 的肾血管收缩作用。数据以均值±SEM 表示,采用方差分析进行分析,P <0.05 为差异有统计学意义。氯沙坦和卡维地洛降低了果糖喂养组的葡萄糖耐量曲线下面积。F 组对 NA、PE、ME 和 Ang II 的反应 (%) 低于 C 组 (F 与 C 相比,17±2 与 38±3;24±2 与 48±2;12±2 与 34±2;17±2 与 26±2)。L 对 NA 和 PE 的反应更高 (P <0.05),而 CV 对 NA、PE 和 Ang II 的反应较 C 减弱 (P <0.05) (L、CV 与 C 相比,47±3、9±2 与 38±3;61±3、29±3 与 48±2;16±3、4±3 与 26±2)。与 F 相比,FL 组而非 FCV 组对 NA、PE 和 ME 的反应增强 (FL 与 F 相比,33±3 与 17±2;45±3 与 24±2;26±3 与 12±2)。氯沙坦和卡维地洛对果糖诱导的胰岛素抵抗有重要的改善作用。氯沙坦治疗可能是恢复果糖喂养大鼠肾循环正常血管反应的有效工具。