Knockdown of parathyroid hormone related protein in smooth muscle cells alters renal hemodynamics but not blood pressure.

Knockdown of parathyroid hormone related protein in smooth muscle cells alters renal hemodynamics but not blood pressure.
Am J Physiol Renal Physiol. 2013 May 29;
Authors: Raison D, Coquard C, Hochane M, Steger J, Massfelder T, Moulin B, Karaplis AC, Metzger D, Chambon P, Helwig JJ, Barthelmebs M
Abstract
Parathyroid hormone related protein (PTHrP) belongs to vasoactive factors that regulate blood pressure and renal hemodynamics both by reducing vascular tone and raising renin release. PTHrP is expressed in systemic and renal vasculature. Here we wanted to assess the contribution of vascular smooth muscle cell endogenous PTHrP to the regulation of cardiovascular and renal functions. We generated a mouse strain (SMA-CreER(T2)/PTHrP(L2/L2) or premutant PTHrP(SM-/-)) which allows temporally-controlled, smooth muscle targeted PTHrP knockdown in adult mice. Tamoxifen treatment induced efficient recombination of PTHrP floxed alleles, and decreased PTHrP expression in vascular and visceral smooth muscle cells of PTHrP(SM-/-) mice. Blood pressure remained unchanged in PTHrP(SM-/-) mice, but plasma renin concentration and creatinine clearance were reduced. Renal hemodynamics were further analyzed during clearance measurements in anaesthetized mice. Conditional knockdown of PTHrP decreased renal plasma flow and glomerular filtration rate with concomitant reduction in filtration fraction. Similar measurements were repeated during acute saline volume expa...

Source: Am J Physiol Renal P... - May 29, 2013 Category: Urology & Nephrology Authors: Raison D, Coquard C, Hochane M, Steger J, Massfelder T, Moulin B, Karaplis AC, Metzger D, Chambon P, Helwig JJ, Barthelmebs M Tags: Am J Physiol Renal Physiol Source Type: research