IONS, VASCULAR MUSCLE, ENDOTHELIUM, AND HYPERTENSION

离子、血管肌、内皮和高血压

• 批准号: 3349435
• 负责人: HENRY W OVERBECK
• 金额: $ 18.44万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-09-30 至 1990-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3349435
• 关键词: adenosinetriphosphatase; angiotensin /renin /aldosterone hypertension; cell membrane; cellular pathology; human subject; hypertension; membrane permeability; membrane potentials; muscle stimulant; ouabain; pregnancy toxemia /hypertension; renal hypertension; tissue /cell culture; vascular endothelium; vascular resistance; vascular smooth muscle; vasoconstrictors

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.

血管平滑肌（vsm）细胞膜离子 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 体液因素一直是 与这些异常有关 我们建议测试的假设， 在高血压的容量或盐依赖性形式中：1.）循环 因子降低Na、K泵活性和/或改变膜离子 VSM中的渗透性; 2.）这种作用导致正性肌力作用， 除非额外的Na，K-ATP酶分子被循环中的 物质;和3.）内皮细胞在反应中起介导作用 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86 Rb和22 Na摄取和流出（3 H）-哇巴因 结合、细胞Na+、K+和H2O。 我们还将使用高电阻（10 十亿欧姆），单通道离子膜片钳技术，我们最近 开发用于研究培养的vsm中的膜离子通道， 高血压血浆和组分对这些通道的影响。 此外，我们将使用交叉灌注技术， [3 H]-哇巴因与完整动脉的结合。 高血压的形式，我们将 研究包括早期和慢性阶段单肾，单夹高血压， 大鼠，1-肾，犬1-包裹性高血压，和原发性， 高醛固酮血症和先兆子痫高血压。