title: Effect of chlorpropamide on water and urea transport in the inner medullary collecting duct.
abstract: The present in vitro microperfusion study examined whether chlorpropamide (CPM) has a direct effect on hydraulic conductivity (Lp x 10(-6) cm/atm.sec) and 14C-urea permeability (Pu x 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(-4) M) 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 less than 0.01) and in the DI rats from 0.05 +/- 0.01 to 5.95 +/- 0.84 (p less than 0.01), but had no effect when it was added to the perfusate. CPM stimulated Lp in a dose-dependent manner with the threshold effect at 10(-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 microU/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.
authors.affiliation: Departamento de Clínica Médica, Faculdade de Medicina, Universidade de São Paulo, Brasil.
authors.forename: A S
authors.initials: AS
authors.lastname: Rocha
authors.forename: W C
authors.initials: WC
authors.lastname: Ping
authors.forename: L H
authors.initials: LH
authors.lastname: Kudo
mesh_terms: D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002747:Chlorpropamide / Q000494:pharmacology*; D003919:Diabetes Insipidus / Q000235:genetics / Q000503:physiopathology*; D004231:Diuresis / Q000187:drug effects; D007685:Kidney Tubules, Collecting / Q000187:drug effects* / Q000378:metabolism; D009995:Osmosis / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D014508:Urea / Q000378:metabolism*; D014867:Water / Q000378:metabolism*; D014882:Water-Electrolyte Balance / Q000187:drug effects*
chemical_list: D014867:Water; D014508:Urea; D002747:Chlorpropamide