Kidney collecting-duct-derived vasopressin is not essential for appropriate concentration or dilution of urine

Am J Physiol Renal Physiol. 2024 May 2. doi: 10.1152/ajprenal.00057.2024. Online ahead of print.ABSTRACTWe previously showed that kidney collecting ducts make vasopressin. However, the physiologic role of collecting-duct-derived vasopressin is uncertain. We hypothesized that collecting-duct-derived vasopressin was required for appropriate concentration of urine. We developed a vasopressin conditional knockout mouse model wherein Cre recombinase expression induces deletion of Avp exon 1 in the distal nephron. We then used age-matched 8 - 12 week old Avp fl/fl;Ksp-Cre(-) (WT) and Avp fl/fl;Ksp-Cre(+) mice for all experiments. We collected urine, serum, and kidney lysates at baseline. We then challenged both WT and KO mice with 24 hour water restriction, water loading, and administration of the vasopressin type 2 receptor (V2R) agonist desmopressin (dDAVP) 1 µg/kg/ip) followed by V2R antagonist OPC-31260 (10 mg/kg/ip). We performed immunofluorescence and immunoblot analysis at baseline and confirmed vasopressin knockout in the collecting duct. We found that urinary osmolality (UOsm), plasma Na+, K+, Cl-, BUN, and copeptin were similar in WT vs KO mice at baseline. Immunoblots of vasopressin regulated proteins Na:K:2Cl cotransporter (NKCC2), Na:Cl cotransporter (NCC) and water channel aquaporin-2 (AQP2) showed no difference in expression or phosphorylation at baseline. Following 24 hour water restriction, WT and KO mice had no differences in UOsm, plasma Na+, K+, Cl-, BUN or cop...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Source Type: research