Project Details

Description

This study will test the hypothesis that, among other factors, the greater
predisposition of blacks than whites to essential hypertension relates to
innate cellular abnormalities of Na+-K+ transport in the former ethnic
group. When present in vascular smooth muscle cells (VSMCs), these
genetically determined abnormalities can produce an increase in the
peripheral vascular resistance and, consequently, hypertension. To explore
this tenet and to exclude the potential effect of extracellular factors, I
propose to study in vitro grown, primary and serially passed, skin
fibroblasts and VSMCs. The skin fibroblasts will be obtained from both
adult and newborn blacks and whites. The VSMCs will be derived from
umbilical arteries of the newborn. The following parameters will be
studied in these cells: a) the activation of the Na+-K+-APTase (ouabain
sensitive ATP hydrolysis) by Na+ and K+, b) the kinetics of 3H-ouabain and
K+ binding to the Na+-pump, c) the activity of the Na+-pump (ouabain
sensitive 86Rb+ uptake and 22Na+ washout), d) the activity of the Na+,
K+-cotransport (bumetanide sensitive 22Na+ and 86Rb+ uptake and washout),
e) the activity of the Na+/H+ antiport (amiloride sensitive 22Na+ uptake
and washout), f) other non-specific Na+ and K+ transport pathways, and g)
the total and exchangeable cellular Na+ and K+ concentrations. These
parameters will also be examined with respect to family history of
essential hypertension in blacks and whites. By comparing abnormalities
identified in cultured VSMCs with those in skin fibroblasts, it will be
possible to determine whether they are specific or generalized.
Correlations will be made between the various Na+-K+ transport parameters,
the cellular Na+ and K+ concentrations and the systemic blood pressure
levels. A myriad of factors have direct or indirect influences on cellular Na+ and
K+ regulation. As blacks and known to differ from whites in their greater
predisposition to essential hypertension and in their handling of Na+ and
K+, it is quite possible that they also differ in the manner by which they
regulate these ions at the cellular level. This project confronts this
possibility in a model of cultured VSMCs and skin fibroblasts. Its finding
will be instrumental in elucidating the etiology of essential hypertension
in blacks.
StatusFinished
Effective start/end date2/1/871/31/90

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

ASJC

  • Medicine(all)

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