Mori Yutaka, Itoh Yohta, Tajima Naoko
Department of Internal Medicine, National Hospital Organization, Utsunomiya National Hospital, Kawachi-gun, Tochigi, Japan.
Am J Hypertens. 2007 Apr;20(4):431-6. doi: 10.1016/j.amjhyper.2006.09.016.
To investigate the influence of blockade of the renin-angiotensin system (RAS) on adipocytes, we compared the effect of telmisartan versus valsartan and amlodipine on adipocyte cellularity in the spontaneously type 2 diabetic, obese rat model.
Male Otsuka Long Evans Tokushima Fatty rats, 8-week-old, were divided into four groups as follows: valsartan (V) group (10 mg/kg, n = 12), telmisartan (T) group (5 mg/kg, n = 12), amlodipine (A) group (2 mg/kg, n = 12), and control (C) group (n = 12). Each drug was mixed with chow and given for 16 weeks.
Although no significant differences were observed in the fasting plasma glucose level between the groups, the fasting plasma insulin level for group T was significantly lower than that for group C. Histopathologic examination showed that the ratio of small adipocytes in groups V and T was significantly higher than that in group C, with the ratio of large adipocytes and the mean adipocyte size shown to be significantly lower in groups V and T than in group C. Furthermore, group T was shown to have a significantly higher ratio of small adipocytes, a significantly lower ratio of large adipocytes, as well as a significantly lower mean adipocyte size, compared to group V.
Although both valsartan and telmisartan downsized adipocytes, adipocyte downsizing was significantly greater with telmisartan compared to valsartan. The likely mechanism for this difference was thought to be the PPAR-gamma-mediated action of telmisartan.
为研究肾素-血管紧张素系统(RAS)阻断对脂肪细胞的影响,我们比较了替米沙坦与缬沙坦及氨氯地平对自发性2型糖尿病肥胖大鼠模型脂肪细胞数量的影响。
将8周龄雄性大冢长-伊-德岛肥胖(Otsuka Long Evans Tokushima Fatty)大鼠分为四组:缬沙坦(V)组(10 mg/kg,n = 12)、替米沙坦(T)组(5 mg/kg,n = 12)、氨氯地平(A)组(2 mg/kg,n = 12)和对照组(C)组(n = 12)。每种药物与饲料混合后给予16周。
尽管各组间空腹血糖水平无显著差异,但T组的空腹血浆胰岛素水平显著低于C组。组织病理学检查显示,V组和T组中小脂肪细胞的比例显著高于C组,V组和T组中大脂肪细胞的比例及平均脂肪细胞大小显著低于C组。此外,与V组相比,T组显示出小脂肪细胞比例显著更高、大脂肪细胞比例显著更低以及平均脂肪细胞大小显著更小。
尽管缬沙坦和替米沙坦均使脂肪细胞缩小,但与缬沙坦相比,替米沙坦使脂肪细胞缩小的程度显著更大。这种差异的可能机制被认为是替米沙坦的过氧化物酶体增殖物激活受体γ(PPAR-γ)介导作用。