Clearance experiments were carried out in pair-fed rats to examine the long-term effects of adrenalectomy and selective adrenal corticosteroid replacement in physiological amounts on renal potassium transport. To this end, clearance studies were conducted in rats that were sham operated, or adrenalectomized (ADX). ADX animals were given either vehicle, aldosterone (0.5 Mig/i00 g body wt per day), dexamethasone (1.2 Mg/i00 g body wt per day), or aldosterone and dexamethasone, by osmotic minipump for 7-9 d whereupon clearance experiments were conducted. After chronic hormone treatment, during basal conditions when only Ringers solution was infused, all groups excreted similar amounts of potassium. However, in all ADX animals without mineralocorticoid replacement, the maintenance of urinary potassium excretion at control levels was associated with hyperkalemia, increased urine flow, and natriuresis; all are factors known to stimulate urinary potassium excretion. During acute potassium infusion, the increase in urinary potassium excretion was less in ADX rats than in controls. This functional deficiency in potassium excretion was partially corrected by dexamethasone and was uniformly associated with a significant increase in urine flow. Aldosterone replacement or aldosterone and dexamethasone given together chronically, sharply increased potassium excretion but did not restore excretion to control levels. Only acute aldosterone infusion (0.2 ,ug/100 g body wt bolus plus 0.2 Mg/100 g body wt per hour), superimposed upon chronic aldosterone and dexamethasone treatment, fully restored potassium excretion to control levels. This aldosterone induced enhancement of potassium excretion, both chronic and acute, was not associated with hyperkalemia, and increased urine flow or natriuresis. Thus, physiological levels of both classes of adrenal corticosteroids stimulate renal potassium excretion albeit by different mechanisms. Mineralocorticoids stimulate tubular potassium excretion directly, whereas glucocorticoids augment excretion indirectly by increasing fluid and sodium delivery along the distal nephron.

This study examines ,ug 100 g-1 * d-1) membrane length increased by 111% compared with control. Dexamethasone treatment, at a level that restored glomerular filtration rate to normal, had no effect on cellular ultrastructure. Combined aldosterone and dexamethasone replacement had no greater effect on basolateral membrane length than aldosterone alone. The length of the luminal membrane of the principal cell type was not affected by ADX or hormone treatment. Intercalated cell membrane length was not affected by ADX or hormone replacement. Thus, chronic aldosterone levels have an important, selective effect on the basolateral membrane of the principal cell. The correlation between these morphological results and the steroid hormone effects on renal electrolyte excretion, reported in the companion paper (15), suggests that basolateral membrane length is an important factor controlling the rate of sodium and potassium transport by the initial collecting tubule.

The effect of insulin on renal potassium excretion was examined by employing the euglycemic insulin clamp technique in combination with renal clearance measurements. While euglycemia was maintained, insulin was infused at rates of 4.8 (n = 7) and 12 (n = 5) mU X kg-1 X min-1. Steady-state plasma insulin levels of 164 +/- 8 and 370 +/- 15 microU/ml were achieved in the low- and high-dose studies, respectively. Base-line plasma potassium concentration declined progressively by a mean of 0.14 +/- 0.09 (P less than 0.05) and 0.40 +/- 0.05 meq/liter (P less than 0.01) during the low- and high-dose insulin infusion protocols. Urinary potassium excretion did not change significantly from base line with either insulin dose. Because the decline in plasma potassium concentration could have masked a stimulatory effect of insulin on UKV, six rats received a 12-mU X kg-1 X min-1 euglycemic insulin clamp in combination with an exogenous potassium infusion to maintain the plasma potassium concentration constant at the basal level (4.03 +/- 0.03 vs. 4.05 +/- 0.05 meq/l). Under these conditions of normokalemia, insulin augmented UKV 2.4-fold, from 0.20 +/- 0.05 to 0.48 +/- 0.04 meq/l (P less than 0.001).

The effect of epinephrine on renal potassium excretion was examined in the rat. In group I KCl was infused acutely to increase plasma K (PK) by 2.0 meq/liter; urinary K excretion (UKV) rose by 1.22 mueq/min. In group II rats, which received a similar dose of KCl but with epinephrine, the increase in PK (delta = 0.8 meq/liter, P less than 0.001) was blunted and UKV was reduced (delta = 0.23 mueq/min, P less than 0.001). To determine whether the reduction in UKV resulted from the smaller increase in PK or from a direct action of epinephrine on renal K transport, a third group of animals received a lower dose of KCl. Despite similar PK levels, the epinephrine group excreted significantly less K in the urine (0.61 vs. 0.93 mueq/min). In group IV propranolol was infused with KCl; UKV was modestly increased. The effects of epinephrine on UKV were unrelated to changes in glomerular filtration rate, urine flow, or UNaV. Micropuncture results showed that at comparable PK levels epinephrine had no direct effect on K secretion by the distal tubule but indirectly inhibited K secretion in this nephron segment by reducing PK. In addition, epinephrine reduced K addition at tubular sites beyond the late distal tubule, most likely in the collecting tubule.

This paper provides (a) a survey of the basic tubule transport mechanisms of sodium and potassium ions along the nephron, (b) a comparison of the overall renal effects of two diuretic agents (torasemide and furosemide), as assessed by renal clearance techniques, (c) an analysis of the tubule sites of action of torasemide evaluated by free-flow micropuncture and microperfusion techniques, and (d) a brief evaluation of some extrarenal transport effects of loop diuretics.