Hypertension Research Unit, Department of Physiology and Pharmacology, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
Metabolism. 2010 Aug;59(8):1200-9. doi: 10.1016/j.metabol.2009.11.013. Epub 2010 Jan 13.
The importance of hypertension treatment has expanded beyond blood pressure management to include additional risk factors, mainly diabetes. It was considered of interest to test the effect of telmisartan, an angiotensin receptor 1 antagonist and peroxisome proliferator activator receptor-gamma partial agonist, on Cohen-Rosenthal diabetic hypertensive nonobese (CRDH) rats, a unique model combining both pathologies. Its effect was examined on fat-derived and inflammatory agents in CRDH. To determine the extent of the drug's peroxisome proliferator activator receptor-gamma modulating beneficial metabolic actions, results were compared with those obtained with valsartan and rosiglitazone in CRDH and Cohen diabetic rat (CDR). Telmisartan and valsartan were given in drinking water at 3 and 12 mg/kg/d, whereas rosiglitazone (3 mg/kg/d) was given as food admixture for a period of 5 months. Blood pressure, glucose, insulin, adiponectin, leptin, and tumor necrosis factor alpha were examined. Telmisartan and valsartan significantly (P < .01) reduced blood pressure, whereas telmisartan and rosiglitazone considerably reduced blood glucose levels to normoglycemic levels (P < .01) in these 2 strains. Insulin levels were not affected by telmisartan and valsartan but were slightly reduced by rosiglitazone in CDR. In contrast to valsartan, adiponectin was significantly (60%, P < .01) increased by telmisartan in both CDR and CRDH, whereas rosiglitazone induced a 60% and 180% increase in CRDH and CDR animals, respectively, on day 30 of treatment. Co-treatment with GW9662 averted telmisartan-induced rise of adiponectin. Tumor necrosis factor alpha declined in telmisartan-treated rats, less so with rosiglitazone, but not valsartan. Telmisartan also induced downsizing of epididymal adipocytes compared with valsartan. Leptin levels were significantly increased by valsartan (P < .05) but reduced by telmisartan and rosiglitazone. The telmisartan-induced increase in adiponectin was most probably associated with a decrease in glucose and tumor necrosis factor alpha levels. Therefore, in addition to its hypotensive effect, telmisartan demonstrated beneficial thiazolidinedione-like effects.
高血压治疗的重要性已经超出了血压管理的范围，包括其他危险因素，主要是糖尿病。因此，测试血管紧张素受体 1 拮抗剂和过氧化物酶体增殖物激活受体-γ部分激动剂替米沙坦对 Cohen-Rosenthal 糖尿病高血压非肥胖 (CRDH) 大鼠的影响是很有意义的，这种大鼠是一种结合了两种病理的独特模型。该研究检测了替米沙坦对脂肪衍生和炎症因子的作用，以确定该药物过氧化物酶体增殖物激活受体-γ调节有益代谢作用的程度，并将结果与替米沙坦、缬沙坦和罗格列酮在 CRDH 和 Cohen 糖尿病大鼠 (CDR) 中的结果进行比较。替米沙坦和缬沙坦分别以 3 和 12mg/kg/d 的剂量加入饮用水中，而罗格列酮 (3mg/kg/d) 则作为食物混合物给药 5 个月。检测了血压、血糖、胰岛素、脂联素、瘦素和肿瘤坏死因子-α。替米沙坦和缬沙坦显著 (P <.01) 降低了血压，而替米沙坦和罗格列酮则将血糖水平显著降低到正常水平 (P <.01)。胰岛素水平不受替米沙坦和缬沙坦的影响，但罗格列酮在 CDR 中略有降低。与缬沙坦不同，替米沙坦在 CRDH 和 CDR 中均显著增加 (60%，P <.01) 脂联素，而罗格列酮在治疗第 30 天分别使 CRDH 和 CDR 动物的脂联素增加 60%和 180%。用 GW9662 共同处理可阻止替米沙坦诱导的脂联素升高。肿瘤坏死因子-α在替米沙坦治疗的大鼠中下降，罗格列酮次之，但缬沙坦则没有。与缬沙坦相比，替米沙坦还诱导了附睾脂肪细胞的缩小。缬沙坦显著增加了瘦素水平 (P <.05)，但替米沙坦和罗格列酮则降低了瘦素水平。替米沙坦诱导的脂联素增加很可能与血糖和肿瘤坏死因子-α水平的降低有关。因此，除了降压作用外，替米沙坦还表现出类似噻唑烷二酮的有益作用。
