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
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