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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL035502-04
Application #
3349440
Study Section
(SRC)
Project Start
1985-09-30
Project End
1989-06-30
Budget Start
1988-09-30
Budget End
1989-06-30
Support Year
4
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of Alabama Birmingham
Department
Type
Overall Medical
DUNS #
004514360
City
Birmingham
State
AL
Country
United States
Zip Code
35294
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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