DIET-INDUCED HYPERINSULINEMIA IN OBESE HYPERTENSION

原发性高血压是一种异质性疾病， 特别是在肥胖人群中，是众所周知的。 阐明高胰岛素血症和胰岛素抵抗的作用 在这种复杂疾病的病因学是一个主要目标， 提议 但这一目标取决于先前的定义， 亚组对抗升压作用的敏感性 减肥. 我们的假设是高胰岛素血症和胰岛素 阻力是“体重”发展的主要因素 肥胖引起的“敏感性”高血压。 本提案将研究胰岛素与 抵抗力和高血压在肥胖患者中的减肥作用 程序（NIH ROL HL 31989），其目的是评估 对减肥的抗升压作用的敏感性。 分析 在那些受试者中实现的血压变化， 重量损失为10%，显示出双峰分布， (plus或减去标准差）舒张压下降23+或 -3mmHg和3 ± 5 mmHg。 拟定研究 旨在证明胰岛素敏感性的变化 根据同时血糖和胰岛素计算的指数（SI） 根据伯格曼的最小模型，数据是预测 血压对体重减轻的反应。 为了证实这一点， 每例患者将在体重减轻后进行研究; 30%的再犯率和第二次减肥也将被研究。 协变量将包括Na+/K+排泄、儿茶酚胺 排泄，血浆肾素活性，血浆心房利钠因子， 体重指数（wt/ht 2）、年龄和性别。 将在Fischer和Zucker中进行同步实验 fa/fa肥胖大鼠喂食高脂肪或高碳水化合物饮食， 描绘一个类似的动物模型。 血流动力学 这些动物的特征将使用 心输出量和局部血流速度的测量， 不同的组织 胰岛素增强血管生成的假说 对急性或慢性容量扩张的自动调节 会得到考验 自动调节（血管阻力反应） 将在基础胰岛素状态下测量， 高胰岛素血症/血糖正常葡萄糖钳夹。 因此，在肥胖动物和人类受试者中进行的平行实验 将被用来测试一个机械假说的作用， 肥胖症中的高胰岛素血症，因为它与原发性高血压有关。

That primary hypertension constitutes a heterogeneous disorder, particularly in the obese population, is well recognized. Elucidation of the role of hyperinsulinemia and insulin resistance in the etiology of this complex disorder is a primary goal of this proposal. But this goal hinges upon the prior definition of distinct subgroups with respect to sensitivity to the anti-pressor effects of weight loss. Our hypothesis is that hyperinsulinemia and insulin resistance are major factors in the development of "weight sensitive" hypertension due to obesity. This proposal will investigate the relationship between insulin resistance and hypertension in obese patients in a weight loss program (NIH ROL HL 31989), an aim of which is to evaluate sensitivity to the anti-pressor effects of weight loss. Analysis of the change in blood pressure achieved in those subjects whose weight loss was 10% reveals a bimodal distribution with mean (plus or minus SD) decline in diastolic blood pressure of 23 plus or minus 3 mmHg and 3 plus or minus 5 mmHg. The proposed study is designed to demonstrate that the change in Insulin Sensitivity Index (SI) calculated from simultaneous blood glucose and insulin data according to the Minimal Model of Bergman, is a predictor of the response of blood pressure to weight loss. To establish this, each patient will be studied after weight loss; a subset of patients with 30% recidivism and a second weight loss will also be studied. Covariates will include Na+/K+ excretion, catecholamine excretion, plasma renin activity, plasma atrial naturetic factor, body mass index (wt/ht2), age and sex. Concurrent experiments will be conducted in Fischer and Zucker fa/fa obese rats fed high fat or high carbohydrate diets in order to delineate an analogous animal model. The hemodynamic characteristics of these animals will be evaluated using measurements of cardiac output and regional blood flow rates in different tissues. The hypothesis that insulin potentiates vascular autoregulation in response to acute or chronic volume expansion will be tested. Autoregulation (response in vascular resistance) will be measured in the basal insulin state, and at two levels of hyperinsulinemic/euglycemic glucose clamps. Thus, parallel experiments in obese animals and human subjects will be used to test a mechanistic hypothesis about the role of hyperinsulinemia in obesity as it relates to primary hypertension.