Project Details


The objective of this project is to test the hypothesis that platelets of
patients with essential hypertension exhibit increased sensitivity to
agonists that exert their effect through the Ca messenger system. This
sensitivity would be expressed by a higher cytosolic free Ca (Cai)
response. It may reflect a higher agonist mediated Ca entry or
mobilization, inappropriate response of the Ca-ATPase and the Na-H antiport
feedback system or both. To explore these alternatives, platelets and
their plasma membrane fractions (i.e., the external plasma and dense
tabular system membranes) from hypertensives and nonmotensives will be
examined under basal conditions and after treatments by agonists and
experimental perturbations that are known to: 1) raise Cai, 2) stimulate
phospholipase C (PLC), and 3) activate the Na-H antiport via protein kinase
C dependent and independent mechanisms. The role of extracellular and
intracellular Ca in possible differences of Cai homeostasis between
platelets from hypertensives and normotensives will be evaluated by
performing experiments in the presence and absence of extracellular Ca, in
the presence of Ca channel blockers and Ca ionophores, and after the
quenching of cellular Ca.

Kinetics of activation of Ca-ATPase in the external plasma membrane,
activation of the Na-H antiport and measurement of Ca in intact platelets,
will be performed using fluorescent methods. The fluorescent probes 2',
7'-bis (carboxyethyl)-5, 6'carboxyfluorescein (BCECF) and fura-2 will be
respectively used for the measurements of cytosolic pH and Cai.

Results of these studies will be instrumental in gaining a better insight,
at the cellular level, into the pathophysiology of essential hypertension.
Understanding the links between abnormalities in the cellular regulation of
Cai and elevated blood pressure will aid in formulating the appropriate
approaches to prevent and treat essential hypertension.
Effective start/end date8/1/907/31/93


  • National Heart, Lung, and Blood Institute


  • Pathophysiology


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