Aim: 

Prostaglandins have been suggested to support urine concentrating aiblity through stimulation of hypothalamic vasopressin (AVP). It was hypothesized that cyclooxygenase-2 (COX-2) activity promotes urine concentrating ability through stimulation of AVP release in response to water deprivation (WD).

Methods: 

To address this, water balance, central AVP mRNA and peptide level, AVP plasma concentration and AVP-regulated renal transport protein abundance were measured in COX-2 deficient mice (COX-2^-/-) and wild-type (WT) mice after 24h WD.

Results: 

In male COX-2^-/- mice, basal urine output and water intake were elevated while urine osmolality was lower compared to WT. Water deprivation resulted in higher plasma osmolality and Na⁺ concentration in COX-2^-/- mice with no gender difference. Hypothalamic AVP mRNA level increased in WT and COX-2^-/- mice after WD. AVP peptide content was higher in COX-2^-/- mice compared to WT and did not change after WD. Baseline plasma AVP concentration in pooled plasma from 8 conscious catheterized WT mice was 0.7 pg/ml and it increased to similar levels after WD: 32.0 ± 6.4 pg/ml in COX-2^-/- and 46.8 ± 14.0 pg/ml in WT. Baseline medullary interstitial osmolality was higher in COX-2^-/- mice and increased similarly in WT and COX-2^-/- after WD. AVP V2 receptor protein abundance in inner medulla (IM) and cAMP urine excretion was lower in COX-2^-/- mice after WD. Baseline abundance of aquaporin-2 (AQP2) was unchanged while pS256-AQP2 in IM was increased in COX-2^-/- after WD, suggesting COX-2 independent regulation of AQP2 expression.

Conclusion: 

in conclusion, COX-2^-/- mice exhibit a mild nephrogenic diabetes insipidus with intact regulation of AVP in response to WD.