Intrarenal urea and electrolyte concentrations as influenced by water diuresis and by hydrochlorothiazide

Abstract

Concentrations of urea, ammonium, sodium and potassium as well as water content were measured in the renal papilla, medulla and cortex, the heart muscle, plasma and urine of rats, in the dehydrated state, the non-diuretic state and after 3 or 8 hr of sustained brisk water diuresis. The same measurements were made on rats which had received a natriuretic dose of hydrochlorothiazide during the 8th hr of water diuresis. Water content of renal tissue increased from cortex to inner medulla in all conditions. In hydrated rats the water content of all layers of renal tissue increased during the first 3 hr and remained stable thereafter. “Exaltation” of urea excretion continued during the first 2 hr of water diuresis, but subsided subsequently. Urinary urea concentrations were equal to, or higher than, urea concentrations in papillary water in the dehydrated and in the non-diuretic states. After 3 hr of water diuresis, urea concentrations decreased in all layers of renal tissue. The papillary urea concentration remained consistently higher than the urinary concentration. The papillo-urinary urea gradient of approximately 80 mmol/1 decreased to 19 mmol/1 after 8 hr of water diuresis, and disappeared in continuous water diuresis sustained over 30 days. These data are interpreted as a consequence of sequestration or tissue binding of urea in compartments of different accessibility to water flowing through papillary and medullary tissues. Cortical tissue water contained more urea than plasma, under all conditions investigated. A part of cortical urea may be sequestered in particular compartments. The cortico-papillary sodium concentration profile corresponded to a 2.8–5.1 fold concentration ratio for sodium in the non-diuretic and in the dehydrated states and decreased during 8 hr of water diuresis. The urinary sodium concentration consistently remained much lower than renal or plasma concentrations. The low sodium concentration in cortical tissue water allows an upper limit of approximately 1 2 to be set for the contribution of intratubular fluid to total tissue water. Potassium concentration in papillary tissue water was equal to or lower than cortical potassium concentration and did not change significantly in water diuresis. Calculated urinary osmolalities were higher than measured values in concentrated urine and in plasma, but were equal in dilute urine. The osmolar concentration profiles in renal tissue depended more on urea than on salt concentrations. Urinary ammonium concentration was higher than the papillary concentration in the dehydrated and the non-diuretic state, but lower in water diuresis. Hydrochlorothiazide, in water diuresis, caused a considerable increase in the urinary sodium concentration and excretion, and a slight increase in the urinary potassium excretion, but did not increase urine flow. Hydrochlorothiazide did not cause a significant decrease in the renal clearance of urea under these circumstances, but induced a slight depression of papillary urea concentration.