LONG-TERM REGULATION OF 4 RENAL AQUAPORINS IN RATS

The aquaporins are molecular water channels expressed in the kidney an d other organs. To investigate long-term regulation of renal expressio n of these water channels, we carried out immunoblotting studies using membrane fractions from rat renal cortex and medulla. Both 48-h water restriction in Sprague-Dawley rats and 5-day arginine vasopressin (AV P) infusion in Brattleboro rats caused significant increases in the ex pression levels of two aquaporins, aquaporin-2 and aquaporin-3, while the levels of aquaporin-1 and aquaporin-4 were unchanged. The increase s in aquaporin-2 and aquaporin-3 expression were seen in inner and out er medulla as well as cortex. Ablation of the corticomedullary interst itial osmotic gradient with an infusion of furosemide did not eliminat e the upregulatory response to AVP infusion in Brattleboro rats. Furth ermore, 5-day furosemide infusion to Sprague-Dawley rats did not decre ase expression levels of the collecting duct aquaporins, but rather in creased them. We conclude that the expression of aquaporin-2 and aquap orin-3, but not aquaporin-1 or aquaporin-4, is increased in response t o elevated circulating AVP. Because regulation of aquaporin-2 and aqua porin-3 levels was observed in the cortex and because osmotic gradient ablation did not abrogate the increase, we conclude that changes in i nterstitial osmolality are not necessary for the AVP-induced upregulat ion of aquaporin-2 and aquaporin-3 expression.