Changes in the tubular reabsorption of sodium independent of aldosterone activity may play an important role in determining sodium excretion. Several studies in the dog employing clearance techniques have demonstrated that infusions of isotonic saline (1-5) or plasma-like solutions (1, 2) result in a depression of the over-all net tubular reabsorption of sodium as the excretion of sodium increases. Dirks, Cirksena, and Berliner have demonstrated by micropuncture studies in the dog that this depression of tubular reabsorption during the infusion of saline occurs specifically in the proximal tubule (6). These same authors reported that acute constriction of the thoracic inferior vena cava, a maneuver known to inhibit sodium excretion and to lead to chronic sodium retention and the formation of ascites (7), prevents this depression of proximal reabsorption during saline infusion (8). Such studies indicate that nonaldosterone factors determining the rate of sodium reabsorption by the proximal tubule could play a major role in the normal physiologic regulation of sodium balance and also may be involved in the pathogenesis of sodium retention in disorders characterized by the accumulation of ascites and edema.Although the factors that determine the rate of proximal tubular reabsorption are unknown, recent studies from our laboratory have demonstrated that renal vascular resistance and perfusion pressure may affect the over-all tubular reabsorp-

Abstract. The importance of plasma protein concentration, renal vascular resistance, and arterial pressure as mediators of the natriuretic response to volume expansion was investigated in anesthetized dogs.Saline loading depressed plasma protein concentration and increased arterial pressure but did not decrease renal vascular resistance. Restoring plasma protein concentration by infusing hyperoncotic albumin increased sodium reabsorption and decreased sodium excretion during saline loading despite simultaneous decreases in renal vascular resistance and increases in arterial pressure.Infusion of "plasma" did not depress plasma protein concentration and produced natriuresis associated with increased arterial pressure and marked decreases in renal vascular resistance. Unilateral hemodynamic natriuresis was produced before "plasma" loading by the renal arterial infusion of acetylcholine, and the subsequent infusion of "plasma" resulted in much smaller increases in sodium excretion by the vasodilated kidney than by the control kidney. If perfusion pressure to both kidneys was then reduced by aortic constriction sodium excretion by the vasodilated kidney could be reduced to preloading (vasodilated) levels without reduced glomerular filtration, despite continued natriuresis in control kidneys which underwent vasodilatation in response to the infusion of plasma.Infusion of equilibrated whole blood did not alter plasma protein concentration or the hematocrit, and renal vascular resistance did not decrease. Sodium excretion was increased minimally or not at all by the infusion of blood despite increased arterial pressure and glomerular filtration. However, in kidneys vasodilated before infusing blood sodium excretion increased in response to tfie infusion in association with increased arterial pressure. This increased excretion of sodium by vasodilated kidneys during infusion of blood could be abolished by reducing perfusion pressure to the preloading level.These observations indicate that changes in plasma oncotic pressure, renal vascular resistance, and arterial pressure either alone or in combination are important variables determining the natriuretic response to volume expansion, and that the relative importance of each of these factors depends on the manner in which volume is expanded (viz., the infusion of saline, plasma, or blood).

Deep intrarenal venous pressure was used as an index of renal capillary pressure to test the proposal that physically induced changes in sodium reabsorption may be mediated by changes in Starling forces across the capillary. Renal vasodilatation produced natriuresis associated with immediate increases in intrarenal venous pressure. Increased arterial pressure was accompanied by further natriuresis and initially increased intrarenal pressure in vasodilated kidneys. Plasma load was always accompanied by increased intrarenal venous pressure. Saline loading usually increased intrarenal venous pressure, and restoration of plasma protein concentration during saline loading reduced, but did not abolish, natriuresis. This continued natriuresis was associated with reduced renal vascular resistance and increased intrarenal venous pressure, demonstrating that continued natriuresis after restoring plasma oncotic pressure during saline loading could relate to increased capillary hydrostatic pressure. Intrarenal venous pressure did not relate to isolated changes in urine flow, arterial pressure, or renal blood flow. These observations support the hypothesis that changes in peritubular capillary hydrostatic pressure initiate changes in tubular sodium reabsorption as a result of changes in capillary uptake.

No abstract

Summary. Anesthetized dogs receiving an infusion of chlorothiazide and ethacrynic acid were given 600-ml infusions of distilled water or dilute dextrose solutions. The absolute rate of tubular sodium reabsorption was depressed, and the glomerular filtration rate was increased during the water loading, despite the associated decreases in plasma sodium concentration and decreases in the filtered load of sodium. The extent to which fractional sodium reabsorption decreased and the excretion of sodium increased was inversely related to the degree to which the filtered load of sodium was depressed as a result of the decreased plasma sodium concentration. We conclude that, in the presence of the diuretic blockade of distal tubular sodium reabsorption, infusion of water depresses proximal tubular reabsorption of sodium and that these changes are qualitatively similar to those previously observed during infusions of saline. Similar depression of tubular reabsorption of sodium and increased excretion of sodium occurred during water loading in the absence of diuretics in dogs undergoing saline diuresis, which presumably provided a high rate of distal sodium reabsorption before water loading.We suggest that volume expansion with water depresses proximal tubular reabsorption of sodium in a manner qualitatively similar to infusions of saline and that the extent to which sodium excretion is increased during water loading is dependent upon 1) the absolute extent to which proximal reabsorption is depressed, 2) the extent to which the filtered load of sodium is maintained in the presence of a falling concentration of sodium in plasma, and 3) the extent to which increased distal reabsorption compensates for the depressed proximal reabsorption of sodium. Mechanisms are suggested whereby the previously reported inverse relationship between plasma concentration of sodium and over-all tubular reabsorption of sodium may be only apparent, and could be the result of physiologic "glomerulotubular balance" during the specific experimental maneuvers.

No abstract

No abstract

To assess in vitro erythropoietic cultures as a tool to discriminate between patients whose anemia improves with and those whose anemia fails to improve with androgens, bone marrows of 24 anemic patients receiving maintenance hemodialysis in hormone-depleted plasma clots were cultured. While erythroid colony proliferation in the presence and absence of androgens by cells of seven patients with good clinical outcomes who were initially studied was similar to that of normal donors, it was reduced (P less than 0.001) in cultures of cells from seven patients whose clinical responses were ultimately poor. Fewer than 25 colonies/6 X 10(4) cells at optimal erythropoietin concentrations, and less than a 25% enhancement in colony growth by androgens were observed in only those cultures derived from clinical nonresponder marrows. Using these criteria, nine of ten prospectively classified patients (five clinical responders and four nonresponders) were identified correctly.