PHYSIOLOGIC MECHANISMS IN STEROID/SALT HYPERTENSION

已知盐皮质激素过量与高盐摄入相结合， 在包括人类在内的几种动物中产生高血压。 尽管 对盐皮质激素盐的作用机制的广泛研究 高血压，导致其发生和维持的因素 目前还不清楚 在这个提议中，对 将在两种品系的大鼠中比较盐皮质激素醛固酮： Wistar大鼠，当用醛固酮治疗时发展为高血压， 盐，以及对这种形式的盐有抵抗力的Wistar-Furth大鼠。 高血压 这些实验代表了研究的独特方法 盐皮质激素盐性高血压，因为它将有可能 确定哪些反应醛固酮可能是重要的， 高血压（仅发生在Wistar大鼠中），以及哪些反应可以 与高血压分离（在两种大鼠品系中均发生）。 增加 离体血管制备物的收缩敏感性 血管收缩剂是这种高血压模型的特征。 我 假设缺乏血管对 血管收缩剂是一种机制， 高血压的大鼠。 此外，我假设， 盐皮质激素-盐 高血压，盐和水潴留，将在威斯特弗斯完好无损 大鼠 为了验证这些假设，我提出了一些实验， 五个具体目标：1）做血管收缩敏感性的变化 （分离的螺旋切割颈动脉），发生在Wistar大鼠治疗 醛固酮和高盐摄入也发生在Wistar-Furth大鼠中，（二） 是血管反应性的变化与降低的 钙来稳定血管平滑肌细胞膜，3)是 醛固酮-盐处理对水和电解质处理的影响 两种菌株相同吗？4)醛固酮结合是否存在差异 血管系统、肾脏或大脑中的部位编号或亲和力？（5） Wistar-Furth大鼠对其他钠依赖性或体积依赖性耐药 实验性高血压的形式 成功完成这些 实验应该产生关于生理学的独特信息 在盐皮质激素盐的发病机制中重要的机制 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.