NUTRITION AND HYPERTENSION: ROLE OF HYPERINSULINEMIA

虽然肥胖是一个已知的危险因素， 高血压，肥胖增加高血压风险的机制 人们对高血压知之甚少。 已经提出 与肥胖相关的高胰岛素血症/胰岛素抵抗 通过刺激交感神经 神经系统，增加肾钠重吸收， 外周血管阻力 这些系统中的更改没有 在肥胖相关高血压的动物模型中得到表征。 本申请的长期目标是了解 肥胖症患者产生高血压的机制。 的具体目标 该应用是：1.来检验和描述 高胰岛素血症/胰岛素抵抗与犬血压的关系 和高血压的啮齿动物模型。2.为了确定是否可变胰岛素 被认为导致胰岛素依赖的系统的敏感性 高血压解释了对肥胖的可变血压反应。 3.研究肾功能、交感神经系统和 局部血管阻力在肥胖相关的动物模型 高血压4.评估高饱和脂肪和低饱和脂肪的作用 饮食在饮食性肥胖和高血压中的表达。 这些 将在整个动物中完成研究。 肌肉对 胰岛素刺激的葡萄糖处理，肾脏对胰岛素刺激的 钠重吸收和交感神经系统对胰岛素 使用高胰岛素钳夹来评估刺激。 肾 功能将通过测量电解质排泄来评估， 控制条件。 SNS活动将通过测量 循环中的儿茶酚胺 心血管功能和局部 将通过放射性微球评估血管阻力 法

Although obesity is a known risk factor for the development of hypertension, the mechanisms by which obesity increase the risk for hypertension are poorly understood. It has been proposed that the hyperinsulinemia/insulin resistance associated with obesity contributes to the development of hypertension by stimulating the sympathetic nervous system, increasing renal sodium reabsorption, and increasing peripheral vascular resistance. Alterations in these systems have not been characterized in animal models of obesity-related hypertension. The long-term objective of this application is to understand the mechanisms which produce hypertension in obesity. The specific aims of this application are: 1. To examine and characterize the relationship between hyperinsulinemia/insulin resistance and blood pressure in canine and rodent models of hypertension. 2. To determine if variable insulin sensitivity of the systems which are thought to cause insulin dependent hypertension explains the variable blood pressure response to obesity. 3. To study changes in renal function, sympathetic nervous system and regional vascular resistance in animal models of obesity-associated hypertension. 4. To assess the role of high versus low saturated fat diet in the expression of dietary obesity and hypertension. These studies will be completed in the whole animal. Sensitivity of muscle to insulin stimulated glucose disposal, of kidney to insulin stimulated sodium reabsorption and of the sympathetic nervous system to insulin stimulation will be assessed using a hyperinsulinemic clamp. Renal function will be assessed by measuring electrolyte excretion under icontrolled conditions. SNS activity will be assessed by measuring circulating catecholamines. Cardiovascular function and regional vascular resistance will be ,assessed by the radioactive microsphere technique.