Influence of lysine-vasopressin dosage on the time course of changes in renal tissue and urinary composition in the conscious rat.

1. The changes in urinary and renal tissue composition induced by continuous, intravenous infusion of lysine-vasopressin (2.5, 5, 15 and 60 mu-u./min. 100 g body wt.) for up to 4(1/2) hr in water-loaded, conscious rats were determined.2. Both the magnitude of, and the time required to attain, maximal and stable responses, in respect to both urinary and tissue composition, varied with the dose.3. The dose-dependent changes in medullary composition were compounded of graded decreases in water content and graded increases in solute (mainly Na and urea) content.4. The relative contribution of the changes in water, Na and urea contents varied with time and with dose. Significant increases in papillary urea content occurred with all doses. The range of change in urea content was wider than that for any other solute.5. At low doses, the changes in urinary flow and osmolality were ascribable, almost entirely, to large decreases in free-water clearance, with minor changes in medullary composition; at higher doses, the increases in urinary osmolality were accompanied by steep increases in medullary solute concentrations.6. A variable, dose-dependent, transient natriuresis occurred during the phase of increasing medullary Na concentration; the peak natriuresis preceded the times of maximal osmolal and Na concentrations in the papilla and urine.7. The differences in osmolal, urea and Na concentrations between papilla and urine also changed with time.8. Both the transitional and steady-state changes induced by lysine-vasopressin are discussed in terms of intrarenal mechanisms. It is concluded that the data are most reasonably interpreted on the basis that several hormone-sensitive loci exist in the kidneys, each with individual dose-response and kinetic characteristics.