Tubular action of diuretics: Distal effects on electrolyte transport and acidification

Abstract

We used clearance and free-flow micropuncture techniques to evaluate the influence of several diuretic agents, given both individually and in various combinations, on transport of sodium, potassium, and fluid, and on acidification and ammonium transport, within the distal tubule of the rat kidney. The loop diuretics, furosemide and piretanide, sharply increased fractional delivery of fluid, sodium, and potassium into the distal tubule, and, as a result, sodium reabsorption and potassium secretion were enhanced in this nephron segment. These two drugs also stimulated urinary acidification and increased urinary phosphate, titratable acid, and ammonium excretion. These effects took place both within the loop of Henle and along the distal tubule. Amiloride and triamterene alone inhibited distal tubular sodium reabsorption and potassium secretion, and, when given with one of the loop diuretics, suppressed both the kaliuresis and the increased acid and ammonium excretion induced by the latter agents. Hydrochlorothiazide and tizolemide inhibited sodium reabsorption within the distal tubule, and were associated with a stimulation of potassium secretion within this segment. Addition of one of these two latter distally acting agents to either of the loop diuretics led to a further augmentation of sodium excretion, but to a reduction of potassium excretion, compared to the responses seen after the loop diuretics alone.

Regulated acid–base transport in the collecting duct

“…Studies in mice lacking either the B1 H + -ATPase subunit (ATP6V1B1) or the alpha subunit of the epithelial Na + channel (ENaC) have shed some light on the importance of the connecting tubule as a major segment (97). Application of loop diuretics increases electrogenic urinary acidification, an effect abolished by inhibitors of ENaC function such as amiloride or triamterene (73). In mice lacking the B1 H + -ATPase subunit, specifically expressed in intercalated cells, urinary pH is more alkaline at baseline and does not acidify upon furosemide application.…”

Renal effects of gastrin C‐terminal tetrapeptide (as pentagastrin) and cholecystokinin octapeptide in conscious rabbit and man

“…However, in rabbits, pentagastrin infusion does not seem to increase plasma vasopressin levels (Unwin, Hanson & Lightman, unpublished observations); although unchanged plasma vasopressin concentrations do not exclude endogenous release (Dixey et al, 1986). Free water clearance can also be affected by altered solute transport in the nephron thick ascending limb: (1) in the absence of changes in vasa recta blood flow, and therefore dissipation of the cortico-medullary solute gradient, inhibition of sodium reabsorption in this segment would impair free water generation, and together with an amiloride or triamterene-like effect on distal tubular sodium reabsorption and potassium secretion, could account for some of the net urinary changes observed (Hropot et al, 1985); (2) increased solute reabsorption in this segment together with increased collecting duct water permeability would be more vasopressin-like, with true urine concentration.…”

Torasemide significantly reduces thiazide-induced potassium and magnesium loss despite supra-additive natriuresis

“…The combination of thiazides with loop diuretics prevents not only the stimulating effect of luminal Na + concentration on NaCl uptake in the early distal tubule, but the thiazides also inhibit carbonic anhydratase (CA) in the proximal tubule, thereby increasing Na + delivery to the TALH [24,[35][36][37]. This is due to the fact that thiazides retain a sulfamyl side group on the benzene ring characteristic of a CA inhibitor such as acetazolamide [36].…”

“…However, in a previous microperfusion study in rats [35], it was shown that thiazides such as HCT or tizolemide increase distal tubular potassium secretion yielding a higher K + excretion than in controls. Yet these kaliuretic agents failed to enhance distal potassium secretion when given together with furosemide or piretanide.…”