Clearance experiments have been performed in 24 subjects with different levels of glomerular filtration, suffering from renal disease without edema, in order to compare the diuretic, saluretic, and kaliuretic responses to a single intravenous injection of meralluride, chlorothiazide, or both together. The inulin clearances of these patients ranged from 5.9 to 135 ml. per minute. The effects of the drugs were studied under constant loading with saline over 3 hours after injection. Our results indicate that over a wide range (15 to 20 ml. per minute up to normal values) a permanent reduction of the glomerular filtration rate has little influence on the diuretic and saluretic effects of meralluride or chlorothiazide. Below 15 to 20 ml. per minute a further reduction results in a sharp decrease in the diuretic and saluretic actions. This can be best explained by assuming that the diuretic agents block an increasing fraction or the tubular reabsorption of water, sodium, and chloride related to the decrease in glomerular filtration rate. This fraction, however, seems to be limited to 30 to 40 per cent of the filtered load. Some dispersion in the glomerulo-tubular activity may account for the splay of the experimental curves. The kaliuretic effect of chlorothiazide is proportional to the glomerular filtration rate. This effect can be blocked by meralluride. At high levels of glomerular filtration the diuretic and saluretic actions of meralluride and chlorothiazide are additive. At lower levels of filtration, such a summation effect is not demonstrable. Apparently, both drugs given together cannot block the reabsorption of more than 30 to 40 per cent of the filtered load. A single injection of chlorothiazide does not lower the arterial blood pressure of hypertensive subjects, loaded with saline, but produces a slight decrease in the glomerular filtration rate, averaging 7 per cent.

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Excretion of infused sodium, chloride, and water increased proportionately in patients with progressively more severe grades of hypertension and of increased renal vascular resistance. These relationships held so long as renal plasma flow and glomerular filtration rate were not greatly impaired. The abnormality was characterized by increased renal tubular rejection of sodium, chloride and water.T HAT most hypertensive patients excrete more water, sodium, and chloride than do normotensive patients when given sodium chloride has been well established since the studies of Farnsworth and Barker. Ellis8 also revealed that sodium output correlated with blood pressure. Both basal sodium excretion and excretion under sodium chloride load were higher in hypertensive than in normotensive individuals. Green, Johnson, Bridges, and liehmann9 classified hypertensive patients as " high salt-exeretors " and " normal salt-exeretors. " High salt-exeretors had an elevated output of salt and water, both under basal conditions and under load, an increased salt appetite, nearly normal glomerular filtration rate maintained in the face of reduced renal plasma flow, and a normal cardiac output. Normal salt-excretors had a normal output of salt and water, both under basal conditions and under load, a normal salt appetite, a marked decrease in glomerular filtration rate and renal plasma flow, and a normal cardiac output. It was suggested that sodium output correlated with the filtration fraction. These findings were interpreted as an indication that "high salt-exeretors" represent an earlier stage of hypertensive disease, whereas "normal salt-exeretors" represent a later stage.

Patients with essential hypertension show an altered renal excretory response to sodium chloride loading. Hypertensive patients acutely eliminate a greater proportion of a salt and water load than do normotensive subjects. This renal abnormality appears to be due to an augmented tubular rejection of sodium chloride and water. This study further defines the nature and extent of this alteration in electrolyte and water metabolism.A PREVIOUS study' confirmed the ob-,&-,Lservations of others2-9 that hypertensive patients excrete more of a parenterally administered sodium chloride load than do normal subjects, and demonstrated that this abnormality was not related to measurable increases in glomerular filtration rate or tubular load of sodium chloride. The present report examines the excretion of sodium chloride and water during the 36-hour period before, during, and after the load of sodium chloride in hypertensive and normotensive subjects. It presents more specific information concerning whether (1) this difference in sodium chloride excretion can also be detected in the resting state before loading, (2) it is found in labile hypertensive patients at the time their blood pressure is normal, and (3)