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H Holdaas

Publications and source records attributed to H Holdaas.

77 records · Page 5Linked to original sources

Re-examination of the dose-reponse relationship for the renal effect of acetozolamide.

To examine the effect of acetazolamide on tubular reabsorption of bicarbonate, plasma concentrations of bicarbonate, potassium and PCO2 were kept constant in volume expanded dogs. Intravenous infusion of acetazolamide reduced glomerular filtration rate (GFR) at all dose levels; after a dose of 30 mg/kg body wt GFR was reduced by about 30% and was not reduced further by increasing the infused dose of acetazolamide up to 500 mg/kg body wt. When control GFR was restored by raising systemic blood pressure, increments in filtered and excreted bicarbonate were not significantly different. At control GFR a linear relationship was obtained between bicarbonate reabsorption and log dose when acetazolamide was administered intravenously in doses ranging between 0.3 and 500 mg/kg body wt (r = 0.93). We conclude that a log dose-reponse relationship applies over a 25 times larger dose range than previously assumed.

Absorption↗

Functional differences of ouabain and ethacrynic acid on renal potassium metabolism in dogs.

Current concepts provide inadequate explanations for the effects of ethacrynic acid (ECA) and ouabain (OUA) on renal potassium metabolism because neither the site of action, nor the tubular effects have been agrreed upon. In the present study on anaesthetized dogs, in vivo inhibitory effects of ECA on mitochondria or Na-K-ATPase were excluded. Firstly, ECA hardly reduced outer medullary metabolic rates in kidneys exposed to OUA and 2,4-dinitrophenol. Secondly, whereas OUA reduced renal Na-KATPase activity by 78% and induced parenchymal potassium release into the renal vein, none of these effects were observed during injection of ECA. During free flow, sodium reabsorption was equally reduced by the two drugs, but fractional potassium excretion was 0.54 +/-0.04 after OUA and 0.99 +/-0.02 after ECA. OUA alone or combined with ECA inhibited almost all ion transport in the distal 60% of the tubular volume as revealed by stop-flow. During ECA alone, chloride reabsorption was reduced more than sodium reabsorption because sodium was exchanged for potassium. ECA and SO4(2-) infusion produced similar stop-flow patterns. Thus, OUA is bound to Na-K-ATPases functionally located to the peritubular cell membrane. ECA promotes potassium secretion probably by inhibiting cellular anion entry at the luminal membrane.

Adenosine Triphosphatases↗