IONS, VASCULAR MUSCLE, ENDOTHELIUM, AND HYPERTENSION

血管平滑肌（VSM）细胞膜离子异常 渗透性和膜 Na、K 泵的活性可能有助于解释 高血压与盐的关系。 体液因素已 与这些异常有关。 我们建议检验以下假设： 在容量或盐依赖性高血压中：1.)\循环 因素降低 Na、K 泵活性和/或改变膜离子 vsm 磁导率； 2.) 此类行为会产生正性肌力作用， 除非循环系统诱导额外的 Na,K-ATP 酶分子 物质； 3.) 内皮细胞在反应中具有介导作用 vsm 对这些体液因素的影响。 我们将测定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 的吸收和流出 (3H)-哇巴因 结合、细胞Na、K和H20。 我们还将使用高电阻（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 中的膜离子通道并进行测定 高血压血浆和分数对这些通道的影响。 此外，我们将使用交叉灌注技术并测量 [3H]-哇巴因与完整动脉结合。 我们将了解高血压的几种形式 研究包括 1 肾、1 夹高血压的早期和慢性阶段 大鼠，1-肾，1-包裹狗高血压，和必需的， 人类高醛固酮血症和先兆子痫高血压。

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.