# Ca2+-Sensing Receptor Mutation and Salt-Sensitive Hypertension

> **NIH NIH SC1** · NORTH CAROLINA CENTRAL UNIVERSITY · 2020 · $324,000

## Abstract

Project Summary
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. We
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. We
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 proposed studies will use Dahl salt-resistant (SR), salt-
sensitive (SS) and CaSR mutant (SS-CasremMcwi) rats. Specific aim 1 will employ protein and DNA analysis to
determine the effect of salt-loading/hypertension on expression of the CaSR, NCX1, G proteins, PKC isoforms
and GRK2 in kidney, dorsal root ganglia (DRG) and mesenteric arteries. Specific aim 2 will employ wire
myography and whole animal studies to determine the effect of salt-loading/hypertension on CaSR signaling
and regulation of vascular and renal Na+/Ca2+ exchange and blood pressure in rats. We believe that these
studies, when completed, will provide a 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 will allow us to continue the current studies, which have
opened up new directions in determining the role of the CaSR in salt-sensitive hypertension. The proposed
studies will also provide training opportunites for under-represented minority students at NCCU to prepare
them for future careers in biomedical research.

## Key facts

- **NIH application ID:** 9881337
- **Project number:** 5SC1HL136278-04
- **Recipient organization:** NORTH CAROLINA CENTRAL UNIVERSITY
- **Principal Investigator:** Emmanuel Modesto Awumey
- **Activity code:** SC1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $324,000
- **Award type:** 5
- **Project period:** 2017-05-01 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9881337

## Citation

> US National Institutes of Health, RePORTER application 9881337, Ca2+-Sensing Receptor Mutation and Salt-Sensitive Hypertension (5SC1HL136278-04). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9881337. Licensed CC0.

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