On the mechanism of diminished urinary carbon dioxide tension caused by amiloride

On the mechanism of diminished urinary carbon dioxide tension caused by amiloride. We investigated under both in vivo and in vitro conditions the mechanism whereby amiloride administration, a model of distal renal tubular acidosis in dogs, decreases the urine-to-blood PCO 2 gradient (U-B PCO 2 ) in alkaline urine. The results demonstrate that U-B PCO 2 is reduced in amiloride-treated dogs as previously reported in rats. The reduction in U-B PCO 2 could not be attributed to amiloride-induced reductions in urinary HCO - 3 concentration since the reduction in U-B PCO 2 was observed over the same range of urinary HCO - 3 concentrations (150 to 250 mEq per liter) as that achieved prior to amiloride administration. U-B PCO 2 correlated positively and linearly with urinary HCO - 3 concentration both prior to (P 2 ]/Δ[HCO - 3 ] u ) of the regression line (P 2 by catalyzing intraluminal dehydration of H 2 CO 3 was excluded by demonstrating that amiloride does not possess carbonic anhydrase activity. The additional possibility that amiloride might facilitate dissipation of carbon dioxide gradients through diffusion (as reported for carbonic anhydrase) was excluded by in vitro studies of the effect of amiloride on carbon dioxide diffusion. These findings suggest that the U-B PCO 2 lowering effect of amiloride is not caused by alterations in urinary [HCO - 3 , CO 2 diffusibility, or alterations in the dehydration rate of H 2 CO 3 thereby providing strong support for the interpretation that reductions in U-B PCO 2 during amiloride administration represent an impairment in distal nephron hydrogen ion secretion. Sur le mechanisme de la diminution de la pression partielle de carbonique dans l'urine determinee par l'amiloride. Nous avons examine in vivo et in vitro le mecanisme par lequel l'administration d'amiloride, un modele d'acidose tubulaire distale chez le chien, diminue le gradient urinesang de PCO 2 (U-B PCO 2 ) en urine alcaline. Les resultats demontrent que U-B PCO 2 est reduit chez le chien traite par l'amiloride comme cela a ete anterieurement montre chez le rat. Le diminution de U-B PCO 2 ne peut pas etre attribuee a la diminution de la concentration urinaire de HCO - 3 determinee par l'amiloride puisque la diminution de U-B PCO 2 a ete observee pour le meme eventail de concentrations urinaires de HCO - 3 (150 a 250 mEq par litre) que celui realise avant l'administration d'amiloride. U-B PCO 2 est correle lineairement et positivement a la concentration urinaire de HCO - 3 aussi bien avant (P 2 ]/Δ[HCO - 3 ]u) de la droite de regression (P 2 urinaire en catalysant la deshydratation intraluminal de H 2 CO 3 a ete exclue par la demonstration de l'absence d'activite de type anhydrase carbonique de l'amiloride. La possibilite que l'amiloride puisse faciliter la dissipation par diffusion des gradients de carbonique a ete exclue par des etudes in vitro. Ces constatations suggerent que l'effet de l'amiloride de diminution de U-B PCO 2 n'est pas lie a des modifications de [HCO - 3 ] de l'urine, de la diffusibilite du carbonique, ou du debit de deshydratation de H 2 CO 3 , et par consequent constituent un argument fort en faveur d'une alteration de la secretion distale d'ion hydrogene.