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Jørgen Frøkiær

Angiotensin II regulates V2 receptor and pAQP2 during ureteral obstruction

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  • Department of Anatomy
  • Biomedical Radio Isotope Techniques
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.
Original languageEnglish
JournalAmerican Journal of Physiology: Renal Physiology
Pages (from-to)F127-F134
Publication statusPublished - 2009

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