PHYSIOLOGIC MECHANISMS IN STEROID-SALT HYPERTENSION

类固醇盐高血压的生理机制

• 批准号: 3473359
• 负责人: CATHY A DAVISON
• 金额: $ 10.59万
• 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/3473359
• 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; 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.

已知盐皮质激素过量与高盐摄入相结合会导致 在包括人类在内的多种动物中产生高血压。 尽管 对盐皮质激素盐机制的广泛研究 高血压，有助于其发生和维持的因素 目前还不清楚。 在这个提议中，生理反应 将在两种大鼠品系中比较盐皮质激素醛固酮： Wistar 大鼠，在接受醛固酮和 盐和 Wistar-Furth 大鼠，它对这种形式的盐有抵抗力 高血压。 这些实验代表了一种独特的研究方法 盐皮质激素盐高血压，因为有可能 确定对醛固酮的哪些反应可能对 高血压（仅发生在 Wistar 大鼠中）以及哪些反应可以 与高血压分开（两种大鼠品系均出现）。 增加 离体血管制剂的收缩敏感性 血管收缩剂是这种高血压模型的特征。 我 假设缺乏增加的血管反应性 血管收缩剂是一种赋予醛固酮盐抵抗力的机制 Wistar-Furth 大鼠的高血压。 此外，我假设 与盐皮质激素盐有关的另一种机制 高血压、盐和水潴留，将在 Wistar-Furth 完好无损 老鼠。 为了检验这些假设，我提出了一些实验来解决 五个具体目标：1）改变血管收缩敏感性 （分离的螺旋状切开的颈动脉）发生在接受治疗的 Wistar 大鼠中 醛固酮和高盐摄入也会发生在 Wistar-Furth 大鼠身上？, 2) 血管反应性的变化与血管的能力下降有关 钙可以稳定血管平滑肌细胞膜？，3）是 醛固酮盐治疗对水和电解质处理的影响 两个菌株相同吗？, 4) 醛固酮结合有差异吗 脉管系统、肾脏或大脑中的位点编号或亲和力？以及 5) Wistar-Furth 大鼠对其他钠依赖性或容量依赖性有抵抗力 实验性高血压的形式？ 顺利完成这些 实验应该产生有关生理的独特信息 盐皮质激素盐发​​病机制中的重要机制 高血压。