Project Details

Description

This project tests the hypothesis that blacks differ from whites in the
cellular regulation of the cytosolic free Ca (Ca-i). Such racial
difference is expressed by enhanced Ca-i turnover and hyperresponsiveness
of American blacks to agonists that act through Ca-i and protein kinase C
(PKC) and it contributes to the increased propensity of blacks to
essential hypertension. Since a rise in Ca-i or increased Ca-i turnover
is associated with an alkaline shift in the cytosolic pH (pH-i) set point
for activation of the Na/H antiport (Xi), it is expected that blacks
would differ from whites not only in Ca-i homeostasis but also in
cellular and systemic Na regulation. Using platelets as a cellular
model, this project focuses on the cellular pathways in control of Ca-i,
PKC and the Na/H antiport in normotensive and hypertensive blacks and
whites of both genders. The following platelet parameters will be
studied in resting platelets and after platelet stimulation with
thrombin, the thromboxane A2 analogue U46619, thymeleatoxin and phorbol
12-myristate 13-acetate (PMA): a) Ca-i, pH-i and cytosolic free Na (Na-i)
profiles, b) Ca influx (using Mn as a Ca surrogate), c) the kinetics of
Ca extrusion (using thapsigargin), d) Xi and activity index of the Na/H
antiport (Zi), e) PKC activity in platelet cytosol and platelet plasma
membranes, and f) density of membrane bound PKC units, derived from the
specific receptors of phorbol 12,13-dibutyrate (PdBu). These parameters
will be examined to elucidate racial and gender-related differences in
Ca-i and their link to altered activities of both PKC and the Na/H
antiport. They will be correlated with the blood pressure profile,
glucose metabolic status, age, indices of body mass and fat distribution,
plasma renin-activity (PRA) and microalbuminuria. Insight into the cellular mechanisms that predispose blacks to essential
hypertension is instrumental for formulating measures to prevent
hypertension in this racial group and for developing specific therapeutic
interventions to attenuate its cardiovascular and renal complications.
StatusFinished
Effective start/end date4/1/937/31/03

Funding

  • National Institutes of Health: $626,953.00
  • National Institutes of Health: $345,405.00
  • National Institutes of Health: $340,138.00
  • National Institutes of Health: $329,081.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $432,384.00
  • National Institutes of Health

ASJC

  • Medicine(all)

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