Effect of long- and short-term antidiuretic hormone availability on internephron heterogeneity in the adult rat.

Abstract

We have previously shown that certain aspects of internephron heterogeneity are reduced or absent in Brattleboro rats with hereditary diabetes insipidus (DI) lacking ADH and can be restored by long-term ADH administration started before complete kidney maturation. In the present study, the effects of long- and short-term availability of ADH in adulthood were studied in Brattleboro DI rats. Single nephron glomerular filtration rate (SNGFR), glomerular volume (GV), and proximal tubular length (PTL) were measured in superficial and juxtamedullary nephrons using the ferrocyanide and microdissection techniques. ADH administration for 6 wk in adult DI rats (group A) restored normal nephron heterogeneity of SNGFR, GV, and PTL by increasing the filtration and size of deep nephrons. Acute changes in ADH availability induced either by 1-h ADH infusion in DI rats (group C) or by ADH discontinuation for 2 days in treated DI rats (group D) did not significantly change the anatomical parameters and only moderately affected SNGFR compared with the preexisting states (groups B and A, respectively). These results suggest that the influence of ADH on internephron heterogeneity is initiated by an increase in deep nephron SNGFR. Based on recent findings concerning the effects of ADH on the medullary (M) part of the thick ascending limbs (TAL), we suggest that the increase in deep nephron SNGFR after ADH may be due to a change in the tubuloglomerular feedback signal at the macula densa resulting from ADH-induced stimulation of the solute reabsorption in the MTAL. Superficial nephrons would be less sensitive to this change due to their long cortical TAL, which removes the macula densa further from the MTAL and provides additional sites for solute reabsorption.