Knockdown of parathyroid hormone related protein in smooth muscle cells alters renal hemodynamics but not blood pressure.
Fiche publication
Date publication
août 2013
Auteurs
Membres identifiés du Cancéropôle Est :
Pr CHAMBON Pierre, Dr MASSFELDER Thierry, Dr METZGER Daniel
Tous les auteurs :
Raison D, Coquard C, Hochane M, Steger J, Massfelder T, Moulin B, Karaplis AC, Metzger D, Chambon P, Helwig JJ, Barthelmebs M
Lien Pubmed
Résumé
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-CreERT2/PTHrPL2/L2 or premutant PTHrPSM-/-), 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 PTHrPSM-/- mice. Blood pressure remained unchanged in PTHrPSM-/- mice, but plasma renin concentration and creatinine clearance were reduced. Renal hemodynamics were further analyzed during clearance measurements in anesthetized 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 expansion. Saline volume expansion induced a rise in renal plasma flow and reduced filtration fraction; both were blunted in PTHrPSM-/- mice leading to impaired diuresis. These findings show that endogenous vascular smooth muscle PTHrP controls renal hemodynamics under basal conditions, and it is an essential factor in renal vasodilation elicited by saline volume expansion.
Référence
Am J Physiol Renal Physiol. 2013 Aug 1;305(3):F333-42