Impaired cyclic AMP generation in outer medullary tubules of gentamicin-treated rats.

We have examined the effects of chronic gentamicin treatment on arginine8-vasopressin (AVP)-dependent cyclic AMP (cAMP) metabolism in rat medullary collecting tubules (oMCT) and medullary thick ascending limbs of Henle's loop (mTALH). Gentamicin attenuated AVP-stimulated cAMP accumulation to a greater extent in the mTALH (delta -51%) than in the oMCT (delta -25%). The mechanism of attenuation differed between segments, and could not be attributed to either direct inhibition of adenylate cyclase activity nor direct potentiation of cAMP-phosphodiesterase activity. These data suggest that the gentamicin-induced decrease in renal concentrating ability may be due at least in part to reduced AVP-dependent cAMP accumulation in the oMCT and mTALH.