IONS, VASCULAR MUSCLE, ENDOTHELIUM, AND HYPERTENSION

离子、血管肌、内皮和高血压

• 批准号: 3349440
• 负责人: HENRY W OVERBECK
• 金额: $ 12.32万
• 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 1989-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3349440
• 关键词: adenosinetriphosphatase; angiotensin /renin /aldosterone hypertension; cell membrane; cellular pathology; dogs; human pregnant subject; human subject; hypertension; laboratory rat; membrane channels; membrane permeability; membrane potentials; muscle stimulant; ouabain; pregnancy toxemia /hypertension; renal hypertension; sodium potassium exchanging ATPase; 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）细胞膜离子异常