Indomethacin reverses alpha-2 <u2> inhibition of water permeability (P_F) in rat inner medullary collecting duct (IMCD)

The objective of this study was to determine if prostaglandins play a role in the inhibition of arginine vasopressin (AVP)-stimulated Pp by α₂ agonists in the rat IMCD. Pp was measured via the isolated perfused tubule technique usmg terminal IMCDs from Wistar rats. Results shown below come from two protocols each with five experimental periods conducted in the sequence listed. AU agents were added to the bath: AVP at 220pM, Tndomethacin (Indo) at 1(HM was used to inhibit prostaglandin synthesis, dexmedetomidine (dex) and atipamezole (ati) were used as the selective 2 agonist and antagonist, respectively, both at IQOnM P y frim/sec) values are shown as mean ±se: 1 2 3 4 5 Control AVP AVP+Dex AVP+Dex+Indo AVP+Dex 1±1 247±9 4±2 167±13 7±2 Control AVP AVP+Indo AVP+Indo+Dex AVP+Indo+Dex+Ati 2±1 156±7 202±9 34±4 141 17 significantly different from previous period (p < ,001); n=5 in both protocols These data indicate that ay mediated reduction of AVP-stimulated Pp in the IMCD utilizes prostaglandins. Interestingly, they also indicate that the reduction of Pp by 2 agonists occurs in the presence of prostaglandin synthesis inhibition if the inhibition occurs before the application of the agonist. This study was supported by NSF grant IBN-9507444.