Altered expression of renal aquaporins and Na+ transporters in rats treated with L-type calcium blocker

Nifedipine, a calcium antagonist, has diuretic and natriuretic properties. However, the molecular mechanisms by which these effects are produced are p oorly understood. We examined kidney abundance of aquaporins (AQP1, AQP2, a nd AQP3) and major sodium transporters [type 3 Na/H exchanger (NHE-3); type 2 Na-Pi cotransporter (NaPi-2); Na-K-ATPase; type 1 bumetanide-sensitive c otransporter (BSC-1); and thiazide-sensitive Na-Cl cotransporter (TSC)] as well as inner medullary abundance of AQP2, phosphorylated-AQP2 (p-AQP2), AQ P3, and calcium-sensing receptor (CaR). Rats treated with nifedipine orally (700 mg/kg) for 19 days had a significant increase in urine output, wherea s urinary osmolality and solute-free water reabsorption were markedly reduc ed. Consistent with this, immunoblotting revealed a significant decrease in the abundance of whole kidney AQP2 (47 +/- 7% of control rats, P< 0.05) an d in inner medullary AQP2 (60 +/- 7%) as well as in p-AQP2 abundance (17 +/ - 6%) in nifedipine-treated rats. In contrast, whole kidney AQP3 abundance was significantly increased (219 +/- 28%). Of potential importance in modul ating AQP2 levels, the abundance of CaR in the inner medulla was significan tly increased (295 +/- 25%) in nifedipine-treated rats. Nifedipine treatmen t was also associated with increased urinary sodium excretion. Consistent w ith this, semiquantitative immunoblotting revealed significant reductions i n the abundance of proximal tubule Na 1 transporters: NHE-3 (3 +/- 1%), NaP i-2 (53 +/- 12%), and Na-K-ATPase (74 +/- 5%). In contrast, the abundance o f the distal tubule Na-Cl cotransporter (TSC) was markedly increased (240 /- 29%), whereas BSC-1 in the thick ascending limb was not altered. In conc lusion, 1) increased urine output and reduced urinary concentration in nife dipine-treated-rats may, in part, be due to downregulation of AQP2 and p-AQ P2 levels; 2) CaR might be involved in the regulation of water reabsorption in the inner medulla collecting duct; 3) reduced expression of proximal tu bule Na 1 transporters (NHE-3, NaPi-2, and Na, K-ATPase) may be involved in the increased urinary sodium excretion; and 4) increase in TSC expression may occur as a compensatory mechanism.