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

tion 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. It is generally agreed that the excretion of hypertonic urine is the result of osmotic equi-librium of water between the fluid flowing in the collecting ducts and the adjacent hypertoni