DIGITAL COMPUTER SIMULATION OF THE NEPHRON: THE ACTION OF OSMOTIC DIURETICS

¹ Departments of Pharmacology and Physiology, Northwestern University Medical School, Chicago, Illinois

A simulation model of nephron function was developed in which the loop of Henle acts as the countercurrent multiplier and an active time-limited sodium transport system along the ascending limb of the loop of Henle initiates the "single effect." The vasa recta acts passively as a countercurrent exchanger. Urea gradients are developed in the model through a passive time-dependent redistribution process which operates as a function of the regional osmotic redistribution of water. The steady-state antidiuretic operation of the model results in the development of renal interstitial osmotic profiles and in tubular filtrate-to-plasma ratios of inulin, electrolytes and urea that correspond closely with experimental data. Perturbations of the simulation model corresponding to some proposed mechanisms of saline-and mannitol-induced diuresis also result in a close correspondence between the model and experimental data, allowing further evaluation of these proposed mechanisms.