Calcium‐sensing receptor (CaSR) expression and Renin/Angiotensin System (RAS) in salt‐sensitive rats

Abstract

The CaSR provides the primary mechanism for Ca2+‐mediated regulation of the release of parathyroid hormone (PTH) as a result of parathyroid cells sensing small changes in the [Ca2+]. However, the CaSR is also involved in the fine regulation of serum Ca2+ levels and renal Ca2+ excretion, independent of PTH secretion. The mechanisms underlying these latter effects are not clear. The renin‐angiotensin system (RAS) plays vital roles in the development of hypertension. The disease is associated with vasoconstriction, endothelial and renal dysfunction. Treatment of the disease is difficult because the mechanisms are not fully understood. Recent studies have revealed that a high salt diet reduces renal [Ca2+] and increases systolic blood pressure in Dahl salt‐sensitive rats. Studies show that adequate Ca2+ intake (1.0 to 1.5 g/day) is critical for optimal blood pressure (BP) regulation, and randomized controlled trials have revealed significant reductions in hypertension risk and BP levels in human. In the kidney, the CaSR is expressed along the nephron and plays an important role, with the Na+/Ca2+ exchanger (NCX), in the regulation of renal tubular Ca2+, Na+ and water reabsorption. In the present study, we analyzed the effects of high salt diets and receptor mutation on the expression of CaSR, its downstream signaling complements and proteins in the RAS in female Dahl salt‐sensitive rats. Our data indicate that CaSR gene mutation and high salt diets modulate the expression of the CaSR, GRK2, PKCα, NCX1 and RAS proteins in kidney. Thus, CaSR signaling is linked to RAS to control hypertension.Support or Funding InformationNIH Grant SC1 HL136278This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.