Submitted on August 5, 2008
Revised on October 9, 2008
Accepted on October 24, 2008
Angiotensin II regulates V2 receptor and pAQP2 during ureteral obstruction
Anja M Jensen1, Eun Hui Bae2, Robert A Fenton3, Rikke Nørregaard1, Søren Nielsen1, Soo Wan Kim2, and Jorgen Frokiaer1*
1 University of Aarhus
2 Department of Internal Medicine
3 The Water and Salt Research Center
* To whom correspondence should be addressed. E-mail: jf{at}ki.au.dk.
Release of bilateral ureteral obstruction (BUO) is associated with nephrogenic diabetes insipidus (NDI) and a reduced abundance of the vasopressin-regulated aquaporins. To evaluate the role of the vasopressin type 2 receptor (V2R) we determined V2R abundance in kidneys from rats subjected to 24 h BUO or 24 h unilateral ureteral obstruction (UUO) followed by 48 h release. As angiotensin II type 1 (AT1) receptor blockade attenuates postobstructive polyuria and AQP2 downregulation, we examined the effect of AT1 receptor blockade on AQP2 phosphorylated at serine 256 (pS256-AQP2) and V2 receptor complex abundance in kidney inner medulla (IM). Furthermore, cAMP generation in sodium fluoride and forskolin-stimulated inner medullary membrane fractions was studied after release of BUO. V2R was significantly reduced to 12% of sham levels in IM and to 52% of sham levels in cortex and outer stripe of outer medulla (OSOM) from BUO rats. In UUO rats, V2R abundance in the obstructed kidney IM decreased to 35% of sham levels whereas it was comparable to sham levels in the non-obstructed kidney IM. No significant change was observed in cortex and OSOM. AT1 receptor blockade attenuated V2R, pS256-AQP2 and Gs
protein downregulation in IM and partially reversed the obstruction-induced inhibition of sodium fluoride and forskolin-stimulated cAMP generation in inner medullary membrane fractions from BUO rats. In conclusion V2R downregulation plays a pivotal role in development of NDI after release of BUO. In addition, we show that angiotensin II regulates the V2 receptor complex and pS256-AQP2 in postobstructive kidney IM, probably by stimulating cAMP generation.
