IONS, VASCULAR MUSCLE, ENDOTHELIUM, AND HYPERTENSION

血管平滑肌细胞膜离子异常 膜的通透性和Na，K泵的活性可能有助于解释 高血压与食盐的关系。体液因素一直是 与这些异常有关。我们建议检验以下假设： 容量或盐依赖形式的高血压：1.)循环 S因素降低Na，K泵活性和/或改变膜离子 VSM中的渗透性；2.这种作用会产生正性变力作用， 除非循环诱导额外的Na，K-ATPase分子 物质；3.)内皮细胞在这一反应中起着中介作用 VSM对这些体液因素的影响。 我们将检测高血压血浆组分对离子转运的影响 培养的VSM细胞。我们将测试内皮细胞介导的效应。 测量将包括86Rb和22na的摄取和流出(~3H)-哇巴因 结合，细胞Na，K和H20。我们还将使用高阻力(10 十亿欧姆)，我们最近拥有的单通道离子膜片钳技术 开发用于研究培养的VSM的膜离子通道并检测 高血压血浆及其各组分对这些通道的影响。 此外，我们将使用交叉灌流技术，并将测量 [3H]-哇巴因与完整的动脉结合。高血压的形式，我们将 研究包括早期和慢性1肾、1夹高血压 大鼠，1肾，狗1包高血压，以及必需的， 人类的高醛固酮血症和子痫前期高血压。

Abnormalities in vascular smooth muscle (vsm) cell membrane ion permeability and in the activity of the membrane Na,K pump may help explain the relationship between hypertension and salt. Humoral factors have been implicated in these abnormalities. We propose to test the hypotheses that, in volume- or salt-dependent forms of hypertension: 1.)\circulating factor(s) decrease Na, K pump activity and/or alter membrane ion permeability in vsm; 2.) such actions result in positive inotropic effects, unless additional Na,K-ATPase molecules are induced by the circulating substances; and 3.) endothelial cells have a mediating role in the response of vsm to these humoral factors. We will assay hypertensive plasma fractions for effects on ion transport of cultured vsm cells. We will test for endothelial-cell-mediated effects. Measurements will include 86Rb and 22Na uptakes and effluxes (3H)-ouabain binding, cell Na+, K+, and H20. We will also use high resistance (10 billion ohms), single-channel ion patch clamp techniques we have recently developed to investigate membrane ion channels in cultured vsm and to assay hypertensive plasma and fractions for effects on these channels. Additionally, we will use cross-perfusion techniques and will measure [3H]-ouabain binding to intact arteries. Forms of hypertension we will study include early and chronic stages of 1-kidney, 1 clip hypertension in rats, 1-kidney, 1-wrapped hypertension in dogs, and essential, hyperaldosteronemic, and pre-eclampsic hypertension in humans.