This study was conducted to determine the quantitative importance of the aldosterone feedback mechanism in controlling each one of three major factors that have often been associated with aldosterone, namely, extracellular fluid sodium concentration, extracellular fluid potassium concentration, and extracellular fluid volume. To do this, the ability of the body to control these three factors in the face of marked changes in daily sodium or potassium intake was studied under two conditions: 1) in the normal dog, and 2) in the dog in which the aldosterone feedback mechanism was prevented from functioning by removing the adrenal glands and then providing a continuous fixed level of supportive aldosterone and glucocorticoids during the low and high electrolyte intake periods. Under these conditions, removal of feedback control of aldosterone secretion decreased the effectiveness of plasma potassium control by nearly fivefold (39% vs. 8% change in plasma potassium concentration), fluid volume by sixfold (12% vs. 2% change in sodium space) and had no effect on control of plasma sodium concentration (2% change with and without feedback control of aldosterone secretion.)

1. Many forms of human and experimental hypertension begin with compromised renal function. Essential hypertension may be another such case. 2. The kidneys of subjects with essential hypertension excrete normal amounts of salt and water at higher-than-normal renal perfusing pressures. Other overt signs of renal dysfunction are few; renal disease is excluded by definition. However, renal blood flow and glomerular filtration rate are usually less than normal in essential hypertension. 3. Renal afferent resistance can be calculated from arterial pressure, renal blood flow, and an estimate of glomerular capillary pressure. These calculations indicate that afferent resistance is increased to two or more times normal in essential hypertension. 4. It is not clear whether afferent constriction causes hypertension or results from it. The ability of high pressure to produce vascular damage points to the latter. But, most essential hypertensives show low-to-normal plasma renin levels and a marked afferent dilation after saline loading. These observations do not suggest nephrosclerosis: they are consistent with a causal role for afferent constriction. 5. We can speculate that, in essential hypertension, there is a defect in one of the mechanisms that sets afferent resistance. Afferent constriction could result from extrinsic influences (neural or humoral) or something totally within the kidney, such as abnormal handling of information from the macula densa. 6. The effect of afferent constriction on salt-and-water excretion would theoretically be offset by elevated arterial pressure so that the actual salt-and-water excretion would be normal, but only so long as the arterial pressure remained elevated.

The purpose of these studies was to compare the effects of proximally and distally acting diuretics on the renal hemodynamic response to protein feeding to determine the importance of the proximal tubule in postprandial renal vasodilation. In chronically instrumented conscious dogs, a meat meal (10 g/kg raw beef) caused glomerular filtration rate (GFR) to increase from 63 +/- 5 to 87 +/- 10 ml/min and effective renal plasma flow (ERPF) to increase from 189 +/- 20 to 249 +/- 20 ml/min, while plasma alpha-amino nitrogen levels rose from 4.0 +/- 0.1 to 6.8 +/- 0.4 mg/dl. Administration of amiloride (0.2 mg/kg + 0.003 mg.kg-1.min-1) or potassium canrenoate (1.76 mg/kg + 1.76 mg.kg-1.h-1), diuretics that act in the distal tubule, had no effect on the renal hemodynamic responses to a meat meal. However, the normal renal hemodynamic responses to protein feeding were abolished during administration of a diuretic that acts in the proximal tubule, acetazolamide (20 mg/kg + 20 mg.kg-1.h-1), although plasma alpha-amino nitrogen levels increased after the meat meal in all experiments. These data suggest that normal proximal tubular sodium reabsorptive function is necessary for acute protein-stimulated renal vasodilation and are consistent with the hypothesis that a tubuloglomerular feedback mechanism may mediate postprandial renal vasodilation.