Effect of chlorpropamide on water and urea transport in the inner medullary collecting duct

摘要

Effect of chlorpropamide on water and urea transport in the inner medullary collecting duct. The present in vitro microperfusion study examined whether chlorpropamide (CPM) has a direct effect on hydraulic conductivity (Lp 10-6 cm/atm sec) and 14C-urea permeability (Pu 10-5 cm/sec) in the middle and distal inner medullary collecting duct (IMCD) obtained from acutely water-loaded Wistar rats and rats homozygous for diabetes insipidus (DI). CPM (10-4M) added to the bath fluid increased the Lp in the water-loaded Wistar rats from -0.05 0.13 to 6.25 0.74 (p -6 M. However, the addition of CPM (10-4 M) to submaximal concentration of VP in the bath fluid did not increase the Lp. Furthermore, CPM was unable to block the inhibitory action of PGE2 on the vasopressin (VP)-stimulated Lp. On the contrary, PGE2 blocked the CPM-stimulated Lp. CPM (10-4 M) in the peritubular fluid was able to cause a significant rise of the Pu from 13.5 0.8 to 17.3 1.0 reversibly, which represented 16% of maximum stimulated effect produced by 50 U/ml of VP. Thus, pharmacological doses of CPM added to the peritubular side have a direct effect on terminal IMCD increasing water and urea permeability in the absence of VP, but this drug does not potentiate the VP-stimulated water transport in the IMCD. Our results were unable to confirm the hypothesis that CPM potentiates the VP-antidiuresis by the inhibition of PGE2 action in the rat IMCD.