Angiotensin II regulates V2 receptor and pAQP2 during ureteral obstruction.
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. Because angiotensin II type 1 (AT1) receptor blockade attenuates postobstructive polyuria and aquaporin-2 (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 nonobstructed kidney IM. No significant change was observed in cortex and OSOM. AT1 receptor blockade attenuated V2R, pS256-AQP2, and G(s)alpha 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 have shown that angiotensin II regulates the V2 receptor complex and pS256-AQP2 in postobstructive kidney IM, probably by stimulating cAMP generation.
Jensen
Anja M
AM
The Water and Salt Research Center, Institute of Clinical Medicine, Univ. of Aarhus, Dept. of Clinical Physiology and Nuclear Medicine, Aarhus Univ. Hospital-Skejby, Brendstrupgaardsvej, DK-8200 Aarhus N, Denmark.
Bae
Eun Hui
EH
Fenton
Robert A
RA
Nørregaard
Rikke
R
Nielsen
Søren
S
Kim
Soo Wan
SW
Frøkiaer
Jørgen
J
D000262:Adenylyl Cyclases / Q000378:metabolism; D000804:Angiotensin II / Q000502:physiology*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D051399:Aquaporin 2 / Q000378:metabolism*; D001562:Benzimidazoles / Q000494:pharmacology; D001713:Biphenyl Compounds; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004195:Disease Models, Animal; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000378:metabolism; D007679:Kidney Medulla / Q000378:metabolism* / Q000473:pathology; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017483:Receptors, Vasopressin / Q000378:metabolism*; D012969:Sodium Fluoride / Q000494:pharmacology; D013777:Tetrazoles / Q000494:pharmacology; D014517:Ureteral Obstruction / Q000378:metabolism* / Q000473:pathology
D047228:Angiotensin II Type 1 Receptor Blockers; C496025:Aqp2 protein, rat; D051399:Aquaporin 2; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D012333:RNA, Messenger; D017483:Receptors, Vasopressin; D013777:Tetrazoles; D000804:Angiotensin II; D005576:Colforsin; D012969:Sodium Fluoride; D000242:Cyclic AMP; D019205:GTP-Binding Protein alpha Subunits, Gs; D000262:Adenylyl Cyclases; C121100:adenylyl cyclase 6; C081643:candesartan