Abstract
To elucidate the mechanism of antidiuretic effect of chlorpropamide (CP) the following studies were performed in diabetes insipidus patients: 1) After a 28-hr water deprivation test, acute CP administration induced a mean UmaxOsm increase of 189 mOsm/kg. On chronic CP therapy there was a mean UmaxOsm increase of 310 mOsm/kg compared to control. 2) On water loading CP induced a reduction in urinary volume with a slight increase in UOsm. 3) Norepinephrine infusion in subpressor doses (0.1 μg/kg/min) inhibited the antidiuresis induced by CP therapy with formation, without any change in GFR. 4) Inability to excrete an acute water load on chronic CP therapy was corrected by oral ethanol or by intravenous diphenylhydantoin. 5) On chronic CP, after decrease in urinary volume, forced H2O intake caused return to pre-therapy urinary volume values, without water intoxication. In compulsive polydipsia, CP administration did not induce any antidiuresis. These results suggest that the presence of endogenous antidiureti...
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