PHYSIOLOGIC MECHANISMS IN STEROID-SALT HYPERTENSION

已知的是，盐摄入量过高与盐皮质激素过多有关 在包括人类在内的几种动物中会产生高血压。尽管 广泛研究糖皮质激素盐的作用机制 高血压的发生和维持因素 目前还不清楚。在这项提议中，对 盐皮质激素醛固酮将在两个品系的大鼠身上进行比较： Wistar大鼠，当使用醛固酮和 盐和Wistar-Furth大鼠，它对这种形式的 高血压。这些实验代表了一种独特的研究方法。 盐皮质激素-盐性高血压，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)以及哪些反应可能 从高血压分离出来的(两个品系的大鼠都有)。增加了 离体血管制剂对血管的收缩敏感性 血管收缩药是这种高血压模型的特征。我 假设血管反应性缺乏对 血管紧张剂是一种对醛固酮盐产生抵抗的机制。 Wistar-Furth大鼠的高血压。此外，我假设 另一种与矿物皮质激素盐有关的机制 维斯塔弗斯的高血压、盐分和水分滞留将完好无损 老鼠。为了检验这些假设，我提出了一些实验，旨在解决 五个具体目标：1)改变血管收缩敏感性 (离体颈动脉螺旋切断)发生在接受治疗的Wistar大鼠 Wistar-Furth大鼠也会出现醛固酮和高盐摄入？，2) 血管反应性的改变是否与运动能力下降有关 钙能稳定血管平滑肌细胞膜吗？，3)是 醛固酮盐处理对水和电解液处理的影响 在两个菌株中是相同的吗？4)醛固酮结合是否有差异 血管系统、肾脏或大脑中的位置编号或亲和力？，以及5) Wistar-Furth大鼠对其他钠依赖或容量依赖的抵抗 实验性高血压的形式？成功完成这些任务 实验应该产生关于生理学的唯一信息 盐皮质激素盐发病机制的研究进展 高血压。

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.