ADH-dependent nephron heterogeneity in rats with hereditary hypothalamic diabetes insipidus

Single nephron glomerular filtration rates (SNGFR) were measured by the [14C]sodium ferrocyanide infusion technique in superficial (S) and juxtamedullary nephrons (JM) of anesthetized Brattleboro rats with or without diabetes insipidus (DI and HZ, respectively). Glomerular volumes (GV) and proximal tubular lengths (PTL) were measured in the same nephrons after microdissection. Glomerular volumes were also assessed in Wistar, HZ, and DI rats in Microfil-injected kidneys. The well-known nephron heterogeneity of the mammalian kidney was absent or greatly reduced in DI compared to HZ rats. S/JM ratios for SNGFR, GV, and PTL averaged 0.71, 0.50, and 0.73 in HZ and 1.04, 0.77, and 0.90 in DI rats. This reduced nephron heterogeneity was due only to reduced dimensions and filtration rates in JM nephrons. The chronic administration of antidiuretic hormone (dDAVP or vasopressin tannate), begun at 2 wk of age and maintained until adulthood (8-10 wk), significantly decreased the S/JM ratios, i.e., restored a nearly normal nephron heterogeneity in DI rats. These results suggest that nephron heterogeneity in the rat kidney is dependent on the presence of antidiuretic hormone, and, more specifically, that ADH and/or its functional consequences can selectively induce an increase in size and filtration rate in deep nephrons.