title: Site and magnitude of the tubular inhibitory effect of expanding the extracellular volume in dogs.
abstract: Ethacrynic acid inhibits energy-requiring transcellular NaCl reabsorption without affecting NaHCO3 reabsorption. Acetazolamide inhibits NaHCO3 and most of the remaining NaCl reabsorption in the proximal tubules (bicarbonate-dependent reabsorption) but raises distal transcellular NaCl reabsorption. After administration of both diuretics, the remaining bicarbonate-dependent and transcellular reabsorptions become constant until glomerular filtration rate (GFR) is almost halved. The inhibitory effect of expanding the extracellular volume (ECV) until plasma volume and GFR increased 30-40% was examined in anesthetized dogs. Examinations at comparable GFR obtained by altering arterial perfusion pressure showed that the inhibitory effect of ECV expansion was attenuated by administering acetazolamide. Ethacrynic acid amplified the inhibitory effect which for sodium and chloride reabsorption amounted to 6-7% of the filtered load at comparable GFR. An inhibitory effect of ECV expansion of bicarbonate reabsorption was disclosed only after raising plasma bicarbonate concentration. Thus, the small inhibitory effect of massive ECV expansion is confined to proximal tubular bicarbonate-dependent reabsorption and is of the same magnitude as previously demonstrated in experiments of similar design by raising plasma pH by only 0.07 unit. Since ouabain inhibits transcellular NaCl reabsorption, a natriuretic hormone is more likely to be an inhibitor of carbonic anhydrase than of Na,K-ATPase.
mesh_terms: D000042:Absorption; D000086:Acetazolamide / Q000494:pharmacology; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism; D004285:Dogs; D004976:Ethacrynic Acid / Q000494:pharmacology; D005110:Extracellular Space / Q000187:drug effects / Q000502:physiology*; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D007684:Kidney Tubules / Q000187:drug effects / Q000502:physiology*; D008297:Male; D010313:Partial Pressure; D012079:Renal Circulation / Q000187:drug effects; D012964:Sodium / Q000378:metabolism; D012965:Sodium Chloride / Q000378:metabolism
chemical_list: D001639:Bicarbonates; D012965:Sodium Chloride; D012964:Sodium; D004976:Ethacrynic Acid; D000086:Acetazolamide