IONS VASCULAR MUSCLE ENDOTHELIUM AND HYPERTENSION

离子血管肌肉内皮和高血压

• 批准号: 3349441
• 负责人: HENRY W OVERBECK
• 金额: $ 17.28万
• 依托单位: WEST VIRGINIA UNIVERSITY
• 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 1991-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3349441
• 关键词: adenosinetriphosphatase; affinity chromatography; angiotensin /renin /aldosterone hypertension; antiport; cell membrane; cellular pathology; dietary mineral; familial hypertension; hypertension; intraocular pressure; laboratory rat; membrane permeability; membrane potentials; muscle stimulant; ouabain; pregnancy toxemia /hypertension; renal hypertension; sodium potassium exchanging ATPase; tissue /cell culture; vascular resistance; vascular smooth muscle; vasoconstrictors; western blottings

Abnormalities in cell membrane ion permeability and in tbe activity of the membrane Na,K pump in vascular smooth muscle (vsm) 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.) endothelial cells have a mediating role in the response of vsm to these humoral factors; 3.) such actions result in positive inotropic effects; 4.) in hypertension in man the decreases in Na,K pump activity are associated with decreases in intraocular pressure; and 5.) increased antiport activity in vsm cells of hypertensives is associated with altered density of Na+-H+ antiport protein. We will assay hypertensive plasma and 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 and cell Na+, K+, and H2O. We will also use high resistance (1010 ohms), single-channel ion patch clamp techniques to characterize 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 to test for humoral inotropic effects and will label vsm cells with antibodies to Na*-H* antiport protein. Forms of hypertension we will study include 1-kidney, 1 clip, DOCA-salt, reduced renal mass, and genetic hypertension and volume-dependent, low renin secondary and primary hypertension

细胞膜离子通透性和tbe活性异常 血管平滑肌(VSM)膜Na，K泵可能有助于解释 高血压与食盐的关系。体液因素一直是 与这些异常有关。我们建议对假设进行检验 这在容量或盐依赖的高血压形式中：1)流通中 S因素降低Na，K泵活性和/或改变膜离子 VSM中的渗透性；2.血管内皮细胞在血管内皮细胞中起中介作用 VSM对这些体液因素的反应；这样的行动会导致 正性肌力作用；在男性高血压患者中， Na、K泵活性与眼压下降有关； 和5.)高血压患者VSM细胞抗转运蛋白活性增强 与Na+-H+逆向转运蛋白密度改变有关。 我们将分析高血压血浆和血浆组分对离子的影响 培养的VSM细胞的运输。我们将测试内皮细胞 细胞介导的效应。测量将包括86Rb和22na吸收 外流和细胞内Na+、K+和H2O。我们还将使用高阻力 (1010欧姆)，单通道离子膜片钳技术 培养的VSM膜离子通道及其对高血压血浆的测定 以及对这些通道的影响的分数。此外，我们将使用 交叉灌流技术测试体液变力作用和意志 用抗Na*-H*反向转运蛋白抗体标记VSM细胞。表格 我们将研究的高血压包括1肾，1夹，DOCA-盐，减少 肾质量、遗传性高血压和容量依赖性低肾素 继发性高血压和原发性高血压