Recent work has demonstrated that the platelet Na/Ca exchanger (NCX) in human beings is identical to the retinal rod NCX. This exchanger plays an important role in regulating platelet Ca stores and it is driven not only by the Na electrochemical gradient but also by the K electrochemical gradient across the platelet plasma membrane. In addition, platelets express the alpha3 isoform of the Na-pump, an isoform with a heightened sensitivity to cardiac glycosides. These features of the platelet ion transport strongly link platelet Ca metabolism to fluctuations in systemic Na and K homeostasis and to the activity of the platelet Na-pump. At the core of this project is the hypothesis that the link between platelet Ca homeostasis and systemic Na/K regulation explains some cardiovascular effects of high Na and high K intakes that are independent of the effects of Na and K intakes on blood pressure.
Three specific aims will explore this hypothesis.
Specific Aim 1 will decipher the physiological and molecular characteristics of the Na-pump in human platelets, focusing on the alpha3 subunit isoform in these cells and its sensitivity to cardiac glycosides. The results will provide a better appreciation of the link between platelet NCX and the Na-pump.
Specific Aim 2 will test the hypothesis that a high Na intake raises cytosolic Na, lowers cytosolic K, and inhibits the NCX to increase platelet Ca stores and platelet reactivity in human beings.
Specific Aim 3 will test the hypothesis that a high K intake lowers cytosolic Na, raises cytosolic K and stimulates platelet NCX activity to diminish platelet Ca stores and platelet reactivity in human beings. Findings of this project might identify previously unknown cardiovascular effects of dietary Na and K, thereby revealing a new dimension of 'salt sensitivity' in human beings.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL063351-03
Application #
6527208
Study Section
Experimental Cardiovascular Sciences Study Section (ECS)
Program Officer
Hasan, Ahmed AK
Project Start
2000-08-15
Project End
2004-07-31
Budget Start
2002-08-01
Budget End
2003-07-31
Support Year
3
Fiscal Year
2002
Total Cost
$353,250
Indirect Cost
Name
University of Medicine & Dentistry of NJ
Department
Pediatrics
Type
Schools of Medicine
DUNS #
605799469
City
Newark
State
NJ
Country
United States
Zip Code
07107
Kimura, Masayuki; Cao, Xiaojian; Aviv, Abraham (2005) Calcium adaptation to sodium pump inhibition in a human megakaryocytic cell line. Am J Physiol Cell Physiol 289:C891-7
Tchakmakjian, L; Gardner, J P; Wilson, P D et al. (2004) Age-dependent telomere attrition as a potential indicator of racial differences in renal growth patterns. Nephron Exp Nephrol 98:e82-8
Aviv, Abraham; Hollenberg, Norman K; Weder, Alan B (2004) Sodium glomerulopathy: tubuloglomerular feedback and renal injury in African Americans. Kidney Int 65:361-8
Benetos, Athanase; Gardner, Jeffrey P; Zureik, Mahmoud et al. (2004) Short telomeres are associated with increased carotid atherosclerosis in hypertensive subjects. Hypertension 43:182-5
Aviv, Abraham; Hollenberg, Norman K; Weder, Alan (2004) Urinary potassium excretion and sodium sensitivity in blacks. Hypertension 43:707-13
Kimura, Masayuki; Lu, Xiaobin; Skurnick, Joan et al. (2004) Potassium chloride supplementation diminishes platelet reactivity in humans. Hypertension 44:969-73
Aviv, Abraham (2002) Telomeres, sex, reactive oxygen species, and human cardiovascular aging. J Mol Med 80:689-95
Aviv, Abraham (2002) Chronology versus biology: telomeres, essential hypertension, and vascular aging. Hypertension 40:229-32
Aviv, Abraham (2002) Salt consumption, reactive oxygen species and cardiovascular ageing: a hypothetical link. J Hypertens 20:555-9
Aviv, A (2001) Hypothesis: pulse pressure and human longevity. Hypertension 37:1060-6