SODIUM PUMP INHIBITORS IN BLOOD PRESSURE REGULATION

工作总结 钠敏感型高血压的起源仍然是 澄清了。钠敏感型高血压的实验模型已被 在实验室动物中创造出来的，其特点是 抑制钠转运的内源性洋地黄样因子(EDLF) 横跨血管平滑肌。我们实验室以前的研究已经 结果表明，卡登内酯(哇巴因类化合物或OLC)和 Bufodienolide(一种类似Marinobufagenin的化合物或MBG)可以被刺激 在大型动物中，通过扩大盐水血浆体积和通过急性 二氧化碳含量增加。这些研究还表明，α-1和α-3 血管平滑肌和神经末梢中Na/K-ATPase的亚型 研究发现，不同的大鼠组织对 各种EDLF。在本年度，盐分的不同影响 大鼠大脑皮质和血浆中OLC和MBG的体积膨胀 并对其进行了分析。在生理盐水输注过程中，血浆MBG水平升高 而血浆OLC则下降。同时，下丘脑和大脑中的OLC 大脑皮层增加，但中枢神经系统MBG无变化。这些 研究结果表明，MBG和OLC都参与了对 循环液量，但OLC在 中枢神经系统，而MBG负责抑制 血管平滑肌Na/K-ATPase的α-1亚型一秒钟 这项研究调查了六周高热的单独和联合影响 钠饮食和社会隔离对大鼠尿MBG的影响。高钠饮食 在隔离的大鼠中，尿MBG增加了两倍，收缩压升高 在整个研究期间，当群养动物的钠负荷 或与正常钠饮食隔离对尿MBG或 血压。对血管平滑肌Na/K泵无长期影响 在任何条件下观察其活性。这项研究表明，高 钠摄入对循环中的蟾蜍二烯内酯EDLF有持续的影响， 但仅有这一效应并不足以抑制血管钠钾泵 长期的活动。未来的研究将集中在这一点上。 OLC和MBG对Dahl高血压患者Na/K泵活性的影响 对高钠饮食的遗传敏感性。此外， 长期服用MBG对血压、OLC、MBG和Na/K泵的影响 将对活动进行调查。

SUMMARY OF WORK The origins of sodium sensitive forms of hypertension remain to be clarified. Experimental models of sodium sensitive hypertension have been created in laboratory animals that are characterized by elevations in endogenous digitalis-like factors (EDLF) that can inhibit sodium transport across vascular smooth muscle. Previous studies in our laboratory have shown that both a cardenolide (a ouabain-like compund or OLC) and a bufodienolide ( a marinobufagenin-like compound or MBG) can be stimulated acutely in large animals by expansion of saline plasma volume and by acute increases in pCO2. These studies have also shown that alpha-1 and alpha-3 isoforms of Na/K ATPase in vascular smooth muscle and nerve endings of rat tissues, respectively, are found to have different sensitivites to various EDLF. During the current year, the differential effects of saline volume expansion on OLC and MBG in brain cortex and blood plasma of rats were analyzed. During saline infusion, plasma levels of MBG increased while plasma OLC decreased. Concurrently, OLC in hypothalamus and brain cortex increased, but central nervous system MBG did not change. These findings indicate that MBG and OLC are both involved in the regulation of circulating fluid volume, but OLC has its predominant effect in the central nervous system, while MBG is responsible for inhibition of the alpha-1 isoform of the Na/K ATPase in vascular smooth muscle. A second study investigated the separate and combined effects of six weeks of high sodium diet and social isolation on urinary MBG in rats. High sodium diet in isolated rats tripled urinary MBG and increased systolic blood pressure throughout the study period, while sodium loading of group-housed animals or isolation with normal sodium diet had no effects on urinary MBG or blood pressure. No long term effects on vascular smooth muscle Na/K pump activity were observed under any condition. This study shows that high sodium intake produce sustained effects on circulating bufodienolide EDLF, but that this effect alone is not sufficient to inhibit vascular Na/K pump activity over the long term. Future research will focus on the role of OLC and MBG in Na/K pump activity in Dahl hypertension, which involves a genetic sensitivity to high sodium diet. In addition, the effects of chronic MBG administration on blood pressure, OLC, MBG and Na/K pump activity will be investigated.