Brian R. Edwards

Compositional Changes of the Corticopapillary Osmotic Gradient during Dehydration in the Absence of Vasopressin

Despite the absence of vasopressin, Brattleboro homozygous (DI) rats concentrate their urine to hypertonic levels when deprived of drinking water. Ultimately this rise in urine osmolality must follow from increased osmolality of the corticopapillary gradient and/or increased osmotic equilibration across the collecting ducts. In this study we examined the concentrations and contents of total solute, urea, and nonurea solute in tissue from cortex to papillary tip of DI rats before and after dehydration for 12, 24, and 48 h. The greatest increase in osmolality occurred during the first 12 h; both urea and nonurea solute concentrations increased, but urea preferentially. From 12 to 48 h there were only small further increases in these concentrations, largely as a result of decreased tissue water content. Osmotic equilibration (reflected by urine/papillary tip osmolality) increased dramatically during dehydration, presumably because of decreased flow rate, attaining full equilibration by 48 h. The rise in urine osmolality during the first 12 h of dehydration was due to increased osmotic equilibration and to the enhanced corticopapillary gradient; urine became more concentrated from 12 to 48 h largely as a result of increased osmotic equilibration.

WATER BALANCE IN THE BRATTLEBORO RAT: SINGLE OR MULTIPLE DEFECTS?*

The total restoration of urinary concentrating ability of the DI rat given daily injections of vasopressin takes several weeks, although complete osmotic equilibrium across the collecting duct is manifest within hours. This suggests that there may be other deficiencies of the renal concentrating mechanism that, if corrected by vasopressin treatment, are corrected more slowly. I have focussed on just three possibilities. First, the morphology of the medullary interstitium is different from normal rats. Perhaps associated with this finding are alterations in the levels of medullary glycosaminoglycans which may have a role to play in water balance. Functional and morphological changes in the juxtamedullary nephrons are also evident. Second, the possibility exists that the countercurrent multiplier of the DI rat operates less efficiently than in the normal animal. Finally, reduced synthesis of PGs in the renal medulla of DI rats may also influence the concentrating mechanism, although in a favorable direction. While most (if not all) of these differences are secondary to the lack of vasopressin, in some instances it appears that it is the high water turnover (possibly the altered chemical composition of the medullary interstitium) that is the primary culprit. While the DI rat remains an excellent model for the study of water balance and the action of vasopressin, the presence of multiple defects within the system should be borne in mind. This is particularly true when comparing data obtained following acute treatment with vasopressin versus that following chronic treatment.

Intramembranous Particle Clusters in Collecting Duct Cells of Rats

Despite the absence of vasopressin, Brattleboro homozygous (DI) rats can concentrate their urine to hypertonic levels when deprived of drinking water. When DI rats are infused with vasopressin, freeze-fracture electron microscopy has revealed increases in intramembranous particle clusters (IPC) in papillary collecting duct luminal membrane that parallel the rise in urine osmolality. In the present study, we examined whether the increase in concentrating ability of DI rats dehydrated for 24 h was associated with a change in IPC. For comparison, oral water loading and 24-hour dehydration were used to suppress and stimulate endogenous vasopressin secretion in Long-Evans (LE) rats, and the effects on urine osmolality and IPC were examined. In LE rats, the induced changes in water balance resulted in alterations in IPC frequency that paralleled urine osmolality, whereas, in DI rats, frequency of IPC remained low under all conditions, even when urine osmolality rose to almost 1,000 mosm/kg H2O as a result of 24-hour dehydration. These results suggest that the increased concentrating ability of dehydrated DI does not depend upon increased water permeability of the papillary collecting ducts.Despite the absence of vasopressin, Brattleboro homozygous (DI) rats can concentrate their urine to hypertonic levels when deprived of drinking water. When DI rats are infused with vasopressin, freeze-fracture electron microscopy has revealed increases in intramembranous particle clusters (IPC) in papillary collecting duct luminal membrane that parallel the rise in urine osmolality. In the present study, we examined whether the increase in concentrating ability of DI rats dehydrated for 24 h was associated with a change in IPC. For comparison, oral water loading and 24-hour dehydration were used to suppress and stimulate endogenous vasopressin secretion in Long-Evans (LE) rats, and the effects on urine osmolality and IPC were examined. In LE rats, the induced changes in water balance resulted in alterations in IPC frequency that paralleled urine osmolality, whereas, in DI rats, frequency of IPC remained low under all conditions, even when urine osmolality rose to almost 1,000 mosm/kg H2O as a result of 24-hour dehydration. These results suggest that the increased concentrating ability of dehydrated DI does not depend upon increased water permeability of the papillary collecting ducts.

Calcium and Sodium Excretion in Rats in Response to Prolonged Treatment with Polythiazide

The hypocalciuric response to prolonged polythiazide (PTZ) administration has been investigated in intact and thyroparathyroidectomized (TPTX) rats. After 3 control days, PTZ was given for 6 days (0.1 mg/100 g body weight . 24 h p.o.). In both groups, calcium excretion fell on day 1 of PTZ and remained depressed thereafter. In the intact rats, this decrease was associated with increased sodium excretion and urine output on treatment day 1. In the TPTX rats, hypocalciuria occurred without change in sodium excretion or body weight; urine output increased on the first 2 days. Thus PTZ can reduce calcium excretion in the absence of parathyroid hormone, changes in sodium excretion, and changes in body weight (an estimate of body fluid balance with constant food intake).

Renal clearances of14C-inulin and polyfructosan in the rat

SummaryPolyfructosan has been used as a substitute for inulin in GFR determinations. However, the validity of this substitution in conditions where renal tubular permeability to other substances, such as mannitol, sucrose and iothalamate, is increased has not been tested. Experiments were performed on 8 rats to compare the clearances of polyfructosan (CPF) and14C-inulin (CIN) during hydropenia, 3% BW saline expansion, elevation of one ureteral catheter by 30 cm, and following return of increased ureteral pressure to the control level. No significant difference between CPF and CIN could be detected except in the kidney subjected to increased ureteral pressure. However, the magnitude of this difference — which may relate to the different molecular weights of the two compounds — was so small that we conclude that the use of CPF, as an index of GFR, is no less reliable than CIN under the conditions tested.

CONCENTRATION OF URINE IN THE ABSENCE OF VASOPRESSIN: EFFECT OF DECREASED RENAL PERFUSION PRESSURE IN CONSCIOUS BRATTLEBORO HOMOZYGOTES

Publisher Summary This chapter summarizes studies which report that when renal perfusion pressure is reduced in conscious Brattleboro homozygotes by constricting the aorta, urine osmolality is raised above that of plasma even though the glomerular filtration rate (GFR) is reduced very little or not at all. This ability to concentrate urine in the absence of vasopressin is not accounted for by an increase in filtration fraction and consequent increased proximal fractional reabsorption, or by a non-antidiuretic hormone (ADH)-mediated increase in water permeability of the distal nephron. It is possible that the capacity to render urine hyperosmotic to plasma in the absence of vasopressin and without a decrease in GFR results from decreased peritubular hydrostatic pressure and a resultant increase in proximal fractional reabsorption and/or a rise in the cortico-papillary interstitial osmotic gradient. However, these possibilities need to be examined further, as the existing Berliner-Davidson hypothesis may also account for the concentration of urine in the absence of vasopressin when the GFR is decreased.