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

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL035502-06
Application #
3349441
Study Section
Cardiovascular and Pulmonary Research B Study Section (CVB)
Project Start
1985-09-30
Project End
1991-09-29
Budget Start
1989-09-30
Budget End
1991-09-29
Support Year
6
Fiscal Year
1989
Total Cost
Indirect Cost
Name
West Virginia University
Department
Type
Schools of Medicine
DUNS #
191510239
City
Morgantown
State
WV
Country
United States
Zip Code
26506
Dubey, R K; Roy, A; Overbeck, H W (1992) Culture of renal arteriolar smooth muscle cells. Mitogenic responses to angiotensin II. Circ Res 71:1143-52
Shoemaker, R L; Worrell, R T (1991) Ca2(+)-sensitive K+ channel in aortic smooth muscle of rats. Proc Soc Exp Biol Med 196:325-32
Kotchen, T A; Zhang, H Y; Covelli, M et al. (1991) Insulin resistance and blood pressure in Dahl rats and in one-kidney, one-clip hypertensive rats. Am J Physiol 261:E692-7
Boegehold, M A; Johnson, M D; Overbeck, H W (1991) Pressure-independent arteriolar rarefaction in hypertension. Am J Physiol 261:H83-7
Overbeck, H W (1990) Digitalis attenuates arterial hypertrophy in experimental hypertension. Proc Soc Exp Biol Med 195:18-21
Overbeck, H W; Magargal, W W (1989) Aortic hypertrophy and ""waterlogging"" in the development of coarctation hypertension. Hypertension 14:316-21
Overbeck, H W; Wallick, E T; Shikuma, R et al. (1988) Hypertensive dog plasma inhibits the Na+-K+ pump of cultured vascular smooth muscle. Hypertension 12:32-8
Liu, J L; Bishop, S P; Overbeck, H W (1988) Morphometric evidence for non-pressure-related arterial wall thickening in hypertension. Circ Res 62:1001-10
Plunkett, W C; Overbeck, H W (1988) Arteriolar wall thickening in hypertensive rats unrelated to pressure or sympathoadrenergic influences. Circ Res 63:937-43
Overbeck, H W (1988) Bioassay by cross-perfusion for circulating inotropic factor in hypertension. Am J Physiol 254:H230-7

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