Cellular adaptation of the rat medullary thick ascending limb to chronic renal failure.

ABSTRACT

Chronic renal failure (CRF) is accompanied by adaptive changes in renal and extrarrenal epithelial ionic transport. Fluid reabsorption in the thick ascending limb of Henle is increased and the capacity to lower the urine osmolality in water diuresis is preserved. To study the cellular mechanism of this adaptation, we measured intracellular cAMP in microdissected medullary thick ascending limb (mTAL) segments in rats with CRF. mTAL exhibited in CRF nephrons an increase of basal cAMP from 6.0 +/- 1.5 in controls to 47.0 +/- 10.3 fmol. mm-1 tubule in CRF (P < 0.05). Maximally stimulated cAMP levels (10(-3) M IBMX plus 10(-5) M Forskolin) were different from basal levels in controls (6.0 +/- 1.5 vs 63.1 +/- 18.8, P < 0.05) but not from basal levels in CRF (47.0 +/- 10.3 vs 63.0 +/- 16.0, P = N.S.). Preincubation with the adenylate cyclase inhibitor 25-dideoxyadenosine (DDA) 10(-4) M produced no changes in cAMP in controls (93.7 +/- 10.3