Villa E, González-Albarrán O, Rábano A, García-Robles R
Department of Endocrinology, Hospital Ramón y Cajal and Universidad de Alcalá de Henares, Madrid, Spain.
J Steroid Biochem Mol Biol. 1999 Apr-Jun;69(1-6):273-9. doi: 10.1016/s0960-0760(99)00045-x.
Human obesity, which is very common in Polycystic Ovaries Syndrome and in "X Syndrome", constitutes an insulin-resistance state in which multiple clinical, biochemical and hemodynamic alterations coexist. Insulin resistance in the obese has been recently associated with an endothelial dysfunction. To investigate the possibility that clinical and metabolic derangements related to insulin resistance could induce changes in vascular blood flows, we have studied the levels of mesenteric (MBF), renal (RBF) and femoral (FBF) blood flows in Beagle dogs kept for 2 years on a normal (control group) or high fat diet (obese group). This experimental model exhibits many of the abnormalities with the human syndrome. In addition, we have tested the effects of chronic treatment with captopril (capto group) in monotherapy or in association with pravastatin (prava+capto group) on the hemodynamic changes associated with this diet. After the two year follow-up, Transonic flow probes were placed around the three arteries to measure basal blood flows and their response to a hyperinsulinemic-normoglycemic test in anesthetized animals. During this test the degree of insulin sensitivity was estimated. In association with higher body weight, blood pressure, insulin resistance, and fasting levels of insulin and total cholesterol, the obese group exhibited decreased basal levels of FBF and a greater femoral vasoconstriction during hyperinsulinism (P < 0.05 vs control). Combined therapy with captopril and pravastatin ameliorated the reduction in basal FBF and hyperinsulinism-induced vasoconstriction (P < 0.05), in addition to the beneficial effects on insulin sensitivity, and clinical and metabolic parameters. Synergistic beneficial effects of both drugs on lipid and carbohydrate profiles may account for this positive outcome, by attenuating the atherogenic process associated with this model.
人类肥胖在多囊卵巢综合征和“X综合征”中非常常见，是一种胰岛素抵抗状态，伴有多种临床、生化和血液动力学改变。肥胖者的胰岛素抵抗最近被认为与内皮功能障碍有关。为了研究与胰岛素抵抗相关的临床和代谢紊乱是否可能导致血管血流变化，我们研究了正常饮食（对照组）或高脂饮食（肥胖组）喂养2年的比格犬的肠系膜血流（MBF）、肾血流（RBF）和股血流（FBF）水平。这个实验模型呈现出许多与人类综合征相似的异常情况。此外，我们还测试了卡托普利单药治疗（卡托组）或与普伐他汀联合治疗（普伐+卡托组）对与这种饮食相关的血液动力学变化的影响。经过两年的随访，在麻醉动物的三条动脉周围放置Transonic血流探头，以测量基础血流及其对高胰岛素-正常血糖试验的反应。在这个试验过程中评估胰岛素敏感性程度。与更高的体重、血压、胰岛素抵抗以及胰岛素和总胆固醇的空腹水平相关，肥胖组的基础FBF水平降低，并且在高胰岛素血症期间股动脉收缩更明显（与对照组相比，P<0.05）。卡托普利和普伐他汀联合治疗改善了基础FBF的降低以及高胰岛素血症诱导的血管收缩（P<0.05），此外还对胰岛素敏感性、临床和代谢参数产生有益影响。两种药物对脂质和碳水化合物谱的协同有益作用可能通过减轻与该模型相关的动脉粥样硬化过程来解释这一积极结果。
