Modulation Of Renin Secretion By Renal Cortical Interstitial Calcium

MODULATION OF RENIN SECRETION BY RENAL CORTICAL INTERSTITIALCALCIUMby DOUGLAS K. ATCHISONMay 2012Advisor: Dr. William BeierwaltesMajor: PhysiologyDegree: Doctor of PhilosophyRenin is secreted from the juxtaglomerular (JG) cells of the afferent arteriole of thekidney, and is the rate-limiting enzyme of the renin-angiotensin system. Renin is quantified invivo as plasma renin activity (PRA). Acutely elevating plasma calcium decreases PRA, but themechanisms by which this occurs is unknown. The overall goal of our study was to determinehow elevated plasma calcium decreases PRA. The calcium-sensing receptor (CaSR) is aubiquitously expressed receptor that translates changes in plasma calcium into changes inintracellular signaling. JG cells are basolaterally bordered by the renal cortical interstitium, andparathyroid hormone (PTH) positively regulates the concentration of calcium in the renalinterstitium. Thus, we hypothesized that hypercalcemia inhibits PRA via PTH-mediated increases in renal cortical interstitial Ca that act on the CaSR triggering Ca-mediated inhibitionof renin secretion. We demonstrated that the CaSR is expressed in JG cells in vivo.Additionally, we demonstrated that acutely stimulating the CaSR with pharmacological agonists decrease basal and stimulated PRA in anesthetized rats in parathyroid-intact andparathyroidectomized (PTX) rats. We demonstrated that acute hypercalcemia decreased PRA, and that this inhibition of PRA is blocked by pharmacological CaSR antagonists and by PTX.