PHYSIOLOGIC MECHANISMS IN STEROID/SALT HYPERTENSION

类固醇/盐高血压的生理机制

• 批准号: 2222362
• 负责人: CATHY A DAVISON
• 金额: $ 11.29万
• 依托单位: ALBANY MEDICAL COLLEGE
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-08-01 至 1996-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2222362
• 关键词: aldosterone; angiotensin /renin /aldosterone hypertension; blood volume; body fluids; calcium flux; dietary excess; disease /disorder model; electrolyte balance; genetic strain; laboratory rat; mineralocorticoids; muscle contraction; nutrition related tag; pathology; salt intake; vascular smooth muscle; vasomotion

Mineralocorticoid excess in combination with high salt intake is known to produce hypertension in several animal species, including humans. Despite extensive investigation into the mechanisms of mineralocorticoid-salt hypertension, the factors that contribute to its genesis and maintenance are as yet unclear. In this proposal, the physiological response to the mineralocorticoid aldosterone will be compared in two strains of rats: the Wistar rat, which develops hypertension when treated with aldosterone and salt, and the Wistar-Furth rat, which is resistant to this form of hypertension. These experiments represent a unique approach to the study of mineralocorticoid-salt hypertension because it will be possible to determine which responses to aldosterone may be important for the hypertension (occur only in Wistar rats) and which responses can be separated from the hypertension (occur in both rat strains). Increased contractile sensitivity of isolated vascular preparations to vasoconstrictors is characteristic of this model of hypertension. I hypothesize that a lack of increased vascular reactivity to vasoconstrictors is a mechanism that confers resistance to aldosterone-salt hypertension on the Wistar-Furth rat. Furthermore, I hypothesize that another mechanism that has been implicated in mineralocorticoid-salt hypertension, salt and water retention, will be intact in Wistar-Furth rats. To test these hypotheses, I propose experiments designed to address five specific aims: 1) do changes in vascular contractile sensitivity (isolated helically-cut carotid arteries) that occur in Wistar rats treated with aldosterone and high salt intake also occur in Wistar-Furth rats?, 2) are changes in vascular reactivity associated with a decreased ability of calcium to stabilize the vascular smooth muscle cell membrane?, 3) are the effects of aldosterone-salt treatment on water and electrolyte handling the same in the two strains?, 4) are there differences in aldosterone binding site number or affinity in the vasculature, kidney, or brain?, and 5) are Wistar-Furth rats resistant to other sodium-dependent or volume-dependent forms of experimental hypertension? Successful completion of these experiments should yield unique information regarding physiological mechanisms that are important in the pathogenesis of mineralocorticoid-salt hypertension.

矿物皮质激素过量与高盐摄入相结合会导致