RESUMEN

The reduction in renal blood flow (RBF) and glomerular filtration rate (GFR) observed after the administration of the carbonic anhydrase inhibitors acetazolamide and benzolamide had been explained as due to activation of the tubuloglomerular feedback mechanism. If correct, pharmacologic blockade of this pathway should prevent the development of renal vasoconstriction with the carbonic anhydrase inhibitors. Thus, the current study evaluates in the dog whole kidney the effect of acetazolamide (20 mg/kg body weight) in the presence or absence of furosemide (5 mg/kg body weight), a drug which blocks the tubuloglomerular feedback. Acetazolamide resulted in a large increase in urinary bicarbonate excretion accompanied by a significant reduction in GFR (16%) and RBF (18%). By contrast with the effects of acetazolamide, furosemide did not alter GFR and increased RBF. In addition, the loop diuretic induced a large chloruresis without changes in urinary bicarbonate excretion. The infusion of acetazolamide in furosemide-treated dogs resulted in a significant increment in renal bicarbonate excretion and in a significant reduction in the levels of both GFR (28%) and RBF (13%). Therefore, furosemide pretreatment did not block the effects of acetazolamide on renal hemodynamic parameters. Consequently, the acetazolamide-induced reduction in both GFR and RBF cannot be accounted for by changes in chloride levels in the juxtaglomerular region due to enhanced salt transport in the macula densa/distal nephron. The increased renal vascular resistance observed with acetazolamide might occur by either a direct effect of this agent on the renal circulation or as a result of changes in intrarenal pressure secondary to the inhibition of proximal fluid reabsorption.

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RESUMEN

The intracellular alkalinization produced when extracellular potassium concentration is increased above its normal levels was studied in the rat diaphragm muscle by determination of the steady-state distribution of [14C]-5,5-dimethyl-2,4-oxazolidinedione (DMO). Replacement of external Na+ with sucrose and Mg2+ or N-methyl-D-glucamine prevented the rise in intracellular pH. Amiloride (1 mM) also abolished the elevation of intracellular pH, while the removal of external Cl- (replaced by gluconate) or addition of 0.1 mM 4-acetamido-4'-diisothyocyanostilbene-2,2-disulfonic acid (DIDS) did not prevent intracellular alkalinization from taking place. These results suggest that in the rat diaphragm muscle a Na(+)-dependent, amiloride-sensitive transport mechanism, perhaps Na+/H+ exchange, plays a major role in the K(+)-induced intracellular alkalinization. This mechanism might account for the metabolic acidosis produced by hyperkalemia.

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1. Counter movements of K+ and H+ across cell membranes were studied in nephrectomized KCl-loaded rats. In one group of animals, the movements of K+ and H+ were determined during and after a KCl load, and in another group, amiloride was used in order to evaluate Na+ participation in K+/H+ exchange. 2. After a KCl load at constant PCO2, 79% of infused K+ left the inulin space, half of which was in exchange for H+. As a result, blood pH fell from 7.40 +/- 0.01 to 7.30 +/- 0.01 (mean +/- SEM; P less than 0.001). 3. During KCl infusion, the K+/H+ exchange ratio varied between 1.3 and 6.8, showing that the coupling ratio is not fixed. 4. Amiloride did not change blood pH and plasma [K+], but prevented the metabolic acidosis produced by the KCl load without affecting K+ entry into the non-inulin space. Therefore, K+ and H+ movements became completely dissociated. 5. The results indicate that KCl activates an amiloride-sensitive H+ extrusion from the cells. This finding is compatible with the view that Na+/H+ exchange participates in the metabolic acidosis produced by a KCl load.

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In five subjects with normal renal function, intravenous dopamine, at a rate of 6 ug/kg/min, produces a renal vasodilation, increase in Na excretion and reduction in urinary osmolality, without modification in glomerular filtration rate. These effects were reversed by intravenous indomethacin (2 mg/kg), suggesting that the renal effects of dopamine might depend on normal prostaglandins production.

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Under the effect of amiloride Na excretion increased and K excretion decreased. These urinary changes were mainly due to alterations in urinary concentration of Na and K with little or no change in urinary volume. Neither plasma Mg concentration nor urinary Mg excretion were modified by the drug. From these results we conclude that, in dogs without Mg loading, Mg transport at distal sites, where amiloride effects take place, is not altered by this diuretic; thus, the change of transepithelial potential difference produced by amiloride would not affect Mg transport.

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RESUMEN

In five subjects with normal renal function, intravenous dopamine, at a rate of 6 ug/kg/min, produces a renal vasodilation, increase in Na excretion and reduction in urinary osmolality, without modification in glomerular filtration rate. These effects were reversed by intravenous indomethacin (2 mg/kg), suggesting that the renal effects of dopamine might depend on normal prostaglandins production.

RESUMEN

Under the effect of amiloride Na excretion increased and K excretion decreased. These urinary changes were mainly due to alterations in urinary concentration of Na and K with little or no change in urinary volume. Neither plasma Mg concentration nor urinary Mg excretion were modified by the drug. From these results we conclude that, in dogs without Mg loading, Mg transport at distal sites, where amiloride effects take place, is not altered by this diuretic; thus, the change of transepithelial potential difference produced by amiloride would not affect Mg transport.