Calcium‐Sensing Receptor Activation In Vivo Decreases Plasma Renin Activity

Abstract

The calcium‐sensing receptor (CaR) transmits changes in extracellular calcium to changes in intracellular signaling and hormonal secretion. The CaR is expressed in many different cell types that indirectly or directly regulate renin secretion including endothelial and vascular smooth muscle cells, as well as the renin‐secreting juxtaglomerular (JG) cells. We have demonstrated that Sensipar, a CaR‐activating calcimimetic, decreases renin release in vitro in primary cultures of JG cells. However, the response to CaR activation on renin secretion in vivo is unknown. As such, we hypothesized that activation of the CaR with Sensipar in vivo would also decrease renin secretion in anesthetized, male Sprague‐Dawley rats. We infused Sensipar i.v. into anesthetized rats at a dose of 60 mg/kg/hr over 60 min. Blood pressure and renal blood flow remained constant at 101±3 mm Hg and 6.21±0.39 ml/min/g kidney weight, respectively, during the infusion of Sensipar. Basal plasma renin activity (PRA) was 15.42 ± 4.41 ngAngI/ml/hr. Sensipar decreased PRA by 58% to 6.53 ± 1.88 ngAngI/ml/hr (p<0.05, n=7). While our result can not necessarily be attributed to the JG cell‐expressed CaR, we conclude that CaR activation inhibits renin secretion in vivo in the absence of changes in renal hemodynamics or blood pressure.