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FAT AND HYPERTENSION

脂肪和高血压

基本信息

批准号：
2028347
负责人：
RUBEN D BUNAG
金额：
$ 16.67万
依托单位：
UNIVERSITY OF KANSAS MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
1993
资助国家：
美国
起止时间：
1993-01-01 至 1999-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/2028347
关键词：
afferent nerve baroreflex cardiovascular function centrally acting drug dietary restriction disease /disorder model disease /disorder proneness /risk essential hypertension exercise hemodynamics hyperinsulinism insulin sensitivity /resistance laboratory rat nutrition related tag obesity radioimmunoassay

项目摘要

Based on results obtained during the current project period, I propose to test the hypothesis that hyperinsulinemia contributes importantly to cardiovascular and baroreflex dysfunction during dietary-induced obesity in rats. Obese rats will be produced by programming pups to overeat and then maintaining them on a high-fat diet immediately after weaning. Blood pressure will be monitored routinely by tail-cuff measurement and any changes thereby detected will be verified by direct intra-arterial recording in the same rats. Initial experiments will determine whether the cardiovascular and baroreflex alterations associated with obesity can be reversed or alleviated by dietary restriction or exercise training. Other experiments will attempt to replicate the cardiovascular and baroreflex impairment in obese rats by chronic intravenous infusion of exogenous insulin in normotensive non-obese rats. Similar measurements will be done during intracerebroventricular infusions to determine whether insulin affects cardiovascular and baroreflex function by acting centrally. Assuming that obesity predisposes rats to hypertension, the additive effects of aortic coarctation or DOCA-salt hypertension in obese rats, or of combining dietary-induced obesity with other predisposing factors will also be studied. My specific aims will be to: (1) establish whether rats with dietary-induced obesity are reasonable models for obesity-hypertension in man by finding out if dietary restriction and/or exercise will restore normal cardiovascular and baroreflex function, (2) record cardiovascular and baroreflex effects of chronic intravenous or intracerebroventricular infusions of insulin in normotensive non-obese rats, and (3) quantify cardiovascular and baroreflex function in before and after induction of aortic-coarctation or DOCA-salt hypertension. By using rats with dietary-induced obesity as models for obesity-hypertension in man, underlying mechanisms can be explored and identified to improve our understanding of how obesity predisposes to hypertension.

根据在本项目期间取得的成果，我提议检验高胰岛素血症对以下因素有重要作用的假设饮食性肥胖的心血管和压力感受性反射功能障碍在老鼠身上。肥胖大鼠将通过编程让幼崽暴饮暴食和然后在断奶后立即保持高脂肪饮食。血压将通过尾部袖带测量和由此检测到的任何变化都将通过直接动脉内检查进行验证在同一只大鼠身上记录。初步实验将确定与肥胖相关的心血管和压力感受性反射改变可以通过饮食限制或运动训练来逆转或减轻。其他实验将尝试复制心血管和慢性静脉滴注阿司匹林对肥胖大鼠压力感受性反射的损害血压正常的非肥胖大鼠的外源性胰岛素。类似的测量方法将在脑室内输液期间进行，以确定胰岛素是否通过作用影响心血管和压力感受器反射功能在中央。假设肥胖使大鼠易患高血压，那么肥胖者主动脉缩窄或DOCA-盐性高血压的相加效应大鼠，或将饮食诱导的肥胖与其他诱因相结合此外，我们亦会研究有关因素。我的具体目标是：(1)建立饮食诱导肥胖的大鼠是否是合理的肥胖-通过发现饮食限制和/或运动将恢复正常的心血管和压力感受器反射功能，(2) 记录慢性静脉或静脉注射对心血管和压力感受性反射的影响血压正常的非肥胖者脑室注射胰岛素以及(3)量化实验前的心血管和压力感受器反射功能。诱导主动脉缩窄或DOCA盐性高血压后。通过用饮食诱导的肥胖大鼠作为动物模型肥胖-男性高血压，潜在的机制可以被探索和确定是为了提高我们对肥胖易感机制的理解高血压。