Verma S, Bhanot S, McNeill J H
Division of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, Canada.
J Pharmacol Exp Ther. 1994 Dec;271(3):1334-7.
In the present study, we examined the relationship between elevated insulin levels and hypertension in the fructose-hypertensive rat model, in which the rise in blood pressure is induced by feeding normal rats a fructose-enriched diet. Six-week-old Sprague-Dawley rats were divided into four experimental groups: control (C, n = 8), control metformin-treated (CT, n = 8), fructose-fed (F, n = 9) and fructose-fed, metformin-treated (FT, n = 10). Long-term oral metformin treatment (500 mg/kg/day) was begun in the CT and FT groups, and 1 week after the initiation of metformin treatment, the F and FT groups started receiving a 66% fructose diet. Metformin treatment prevented the increase in plasma insulin levels in the FT rats (FT, 32 +/- 4 microU; F, 51 +/- 7 microU-ml; P < .001) without any change in plasma glucose levels. Interestingly, metformin treatment also prevented the increase in systolic blood pressure in the FT group (FT, 143 +/- 2 mm Hg; F, 159 +/- 2 mm Hg; P < .001) but had no effect in the CT group (CT, 142 +/- 3 mm Hg; versus C, 141 +/- 2 mm Hg; P > .05). Restoration of plasma insulin levels in the FT group to levels that existed in the untreated F rats reversed the effect of metformin on blood pressure (FT plus insulin, 158 +/- 3 mm Hg; F, 160 +/- 3 mm Hg; P > .05). In conclusion, metformin prevents the hyperinsulinemia and hypertension that occur after feeding normal rats a fructose-enriched diet. Also, the antihypertensive effects of metformin can be reversed by raising the plasma insulin levels in the treated rats to those that exist in the untreated fructose-fed group, which suggests that hyperinsulinemia may contribute toward the increase in blood pressure in this model of experimental hypertension.
在本研究中，我们在果糖诱导高血压大鼠模型中检测了胰岛素水平升高与高血压之间的关系，该模型中正常大鼠通过喂食富含果糖的饮食诱导血压升高。六周龄的斯普拉格-道利大鼠被分为四个实验组：对照组（C，n = 8）、对照二甲双胍治疗组（CT，n = 8）、果糖喂养组（F，n = 9）和果糖喂养二甲双胍治疗组（FT，n = 10）。CT组和FT组开始长期口服二甲双胍治疗（500 mg/kg/天），在二甲双胍治疗开始1周后，F组和FT组开始接受66%果糖饮食。二甲双胍治疗可防止FT组大鼠血浆胰岛素水平升高（FT组，32±4微单位；F组，51±7微单位/毫升；P <.001），而血浆葡萄糖水平无任何变化。有趣的是，二甲双胍治疗还可防止FT组收缩压升高（FT组，143±2毫米汞柱；F组，159±2毫米汞柱；P <.001），但对CT组无影响（CT组，142±3毫米汞柱；与C组，141±2毫米汞柱；P>.05）。将FT组血浆胰岛素水平恢复到未治疗F组大鼠的水平可逆转二甲双胍对血压的影响（FT加胰岛素组，158±3毫米汞柱；F组，160±3毫米汞柱；P>.05）。总之，二甲双胍可预防正常大鼠喂食富含果糖饮食后出现的高胰岛素血症和高血压。此外，通过将治疗大鼠的血浆胰岛素水平提高到未治疗果糖喂养组的水平，可逆转二甲双胍的降压作用，这表明高胰岛素血症可能导致该实验性高血压模型中的血压升高。
