Action of ADH on isolated medullary thick ascending limb of the Brattleboro rat

Establishment of a maximal corticomedullary osmotic gradient during chronic administration of arginine vasopressin (antidiuretic hormone, ADH) to Brattleboro (diabetes insipidus, DI) rats is a gradual process. The effects of ADH on voltage and radioisotopic chloride efflux (lumen to bath) were investigated in medullary thick ascending limb (mTAL) isolated from DI rats and perfused in vitro. Acute in vitro exposure of mTAL to ADH (250 microU/ml) significantly increased both the voltage (+3.3 +/- 0.3 to +4.5 +/- 0.5 mV) and chloride efflux (192.7 +/- 29.4 to 240.4 +/- 41.5 peq/min X mm). After chronic in vivo treatment with ADH for 10-21 days mTAL expressed substantially higher basal voltage and chloride efflux (+8.4 +/- 0.6 mV and 393.2 +/- 71.6 peq/min X mm). Acute in vitro application of ADH to mTAL from chronically treated animals induced a further small increase in voltage (22%). These results are taken to indicate that ADH may have dual effects on NaCl transport by the mTAL of the DI rat: a small rapid effect, and a larger long-term increase in transport that can be shown only after chronic administration of ADH. These effects may, in part, explain the gradual enhancement of concentrating ability observed in DI rats.