The goal of the proposed studies is to determine the mechanism of Ca2+-sensing receptor (CaSR)-mediated vascular relaxation, control of urinary Na+/Ca2+ excretion and their regulation by protein kinase C (PKC) and G protein-coupled receptor kinase 2 (GRK2) in hypertension.
Cardiovascular disease is the leading cause of death and disability in the Western world, and hypertension, which is associated with vasoconstriction, endothelial dysfunction, end organ damage and stroke, is common in the African American community. The researchers for this project have hypothesized that local increases in interstitial calcium concentration induce vasorelaxation by activating the CaSR and subsequent release of a vasodilator(s) to counteract the effects of endothelial dysfunction.
They propose to test the hypothesis that the CaSR mediates vascular relaxation and control of urinary Na+/Ca2+ excretion through the NCX in salt-loading/hypertension, a process regulated by PKC and G protein-coupled receptor kinase 2 (GRK2). Salt-loading/hypertension increases expression and signaling of the CaSR to counteract the high vascular tone as well as decrease Na+ but increase Ca2+ excretion to maintain vascular integrity and decrease Na+ retention.
The researchers believe these studies, when completed, will provide new information on the mechanisms of CaSR-mediated signaling in salt-sensitive hypertension. The proposed studies are integrative and have the potential of identifying targets for the development of novel dietary strategies to counteract hypertension in the short-term and new vasodilator compounds in the long-term.
This award allows them to continue the current studies, which have opened up new directions in determining the role of the CaSR in hypertension. The proposed studies will also provide training opportunities for underrepresented minority students at NCCU to prepare them for future careers in biomedical research.