FAT AND HYPERTENSION

脂肪和高血压

• 批准号: 2219242
• 负责人: RUBEN D BUNAG
• 金额: $ 14.72万
• 依托单位: UNIVERSITY OF KANSAS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-01-01 至 1997-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2219242
• 关键词: afferent nerve; baroreflex; cardiovascular function; centrally acting drug; diet therapy; disease /disorder model; disease /disorder proneness /risk; essential hypertension; exercise; hemodynamics; hyperinsulinism; insulin sensitivity /resistance; laboratory rat; obesity; radioimmunoassay

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.

根据当前项目期间取得的成果，我建议 检验高胰岛素血症重要影响的假设 饮食引起的肥胖期间心血管和压力反射功能障碍 在老鼠身上。 肥胖老鼠将通过对幼鼠进行编程使其暴饮暴食而产生 然后在断奶后立即保持高脂肪饮食。 将通过尾套测量定期监测血压 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 在同一只老鼠身上进行记录。 初步实验将确定是否 与肥胖相关的心血管和压力反射改变可以 通过饮食限制或运动训练可以逆转或缓解。 其他实验将尝试复制心血管和 慢性静脉输注对肥胖大鼠的压力反射损害 正常血压非肥胖大鼠的外源胰岛素。 类似的测量 将在脑室内输注期间进行以确定 胰岛素是否通过作用影响心血管和压力反射功能 集中。 假设肥胖使大鼠易患高血压， 主动脉缩窄或 DOCA 盐高血压对肥胖者的累加效应 大鼠，或将饮食引起的肥胖与其他诱发因素相结合 因素也将被研究。 我的具体目标是：（1）建立 饮食引起的肥胖大鼠是否是合理的模型 通过查明是否存在饮食限制和/或 运动将恢复正常的心血管和压力反射功能，（2） 记录慢性静脉注射或静脉注射对心血管和压力反射的影响 血压正常非肥胖者脑室内注射胰岛素 大鼠，以及（3）量化之前的心血管和压力反射功能 以及诱导主动脉缩窄或 DOCA 盐高血压后。 经过 使用饮食引起的肥胖大鼠作为模型 人类肥胖-高血压的潜在机制可以探索和 确定以提高我们对肥胖如何导致的理解 高血压。