ESCAPE FROM VASOPRESSIN-INDUCED ANTIDIURESIS - ROLE OF VASOPRESSIN RESISTANCE OF THE COLLECTING DUCT

Previously, we demonstrated that escape from vasopressin-induced antid iuresis (''vasopressin escape'') in rats is associated with a large, s elective decrease in whole kidney expression of aquaporin-2, the vasop ressin-regulated water channel. Here, we show that isolated perfused i nner medullary collecting ducts (IMCDs) from vasopressin-escape rats { desamino-[D-arginine]vasopressin (DDAVP)/water-loaded} have dramatical ly reduced vasopressin-dependent osmotic water permeabilities [46% of control rats (DDAVP alone)], which coincides with a fall in inner medu llary aquaporin-2 protein abundance as measured by immunoblotting in t he opposite kidney Furthermore, we demonstrate in IMCD suspensions tha t cAMP accumulation in response to DDAVP is substantially reduced in t he vasopressin-escape rats both in the presence and absence of the pho sphodiesterase inhibitor IBMX. By immunoblotting, we show that the abu ndance of two proteins important in cAMP generation: the stimulatory h eterotrimeric G protein subunit G(s) alpha and adenylyl cyclase type V I, do not change. We conclude that vasopressin escape is associated wi th relative vasopressin resistance of the collecting duct cells manife sted by decreased intracellular cAMP levels. The decreased cAMP levels can contribute to the demonstrated decrease in collecting duct water permeability in two ways: 1)by causing a decrease in aquaporin-2 expre ssion and 2) by limiting the acute action of vasopressin to increase c ollecting duct water permeability.