Effect of acetazolamide on glomerular balance and renal metabolic rate.
Glomerulotubular balance, defined as proportionality between filtered and reabsorbed sodium during inhibition of sodium reabsorption in the thick ascending limb of Henle's loop (diluting segment), was examined in anaesthetized dogs by gradual reduction of renal arterial pressure. In control experiments, glomerulotubular balance applied over the whole rante of glomerular filtration rate (GFR) examined but was absent after acetazolamide administration (30 mg/kg/body wt) at GFR above 50% of control. Hence, the inhibitory effect of acetazolamide varied with GFR. At control GFR, acetazolamide reduced tubular sodium reabsorption by 32 +/- 2% chloride reabsorption by 34 +/- 3%, and bicarbonate reabsorption by 52 +/- 2%; no significant effect was observed at GFR below 50% of control. For each bicarbonate ion, three sodium ions and two chloride ions were inhibited. Measurements of renal oxygen consumption and heat accumulation rates showed that acetazolamide did not reduce renal metabolic rate significantly. It is proposed that energy-requiring hydrogen ion secretion occurs at unchanges rate during variations in GFR but that back leakage of hydrogen ions varies with bicarbonate concentration in tubular fluid. Net secretion of hydrogen ions is associated with bicarbonate transport into the intercellular space and is linked with sodium reabsorption. The concentration difference of bicarbonate salts over the tight junction (zonula occludens), which is much less permeable to bicarbonate than to sodium chloride, provides the osmotic force for reabsorption of water and sodium chloride from the tubular lumen into the intercellular space. Glomerulotubular balance is mediated by variations in filtered amounts of bicarbonate.
D000086:Acetazolamide / Q000494:pharmacology*; D000818:Animals; D001485:Basement Membrane / Q000187:drug effects / Q000378:metabolism; D001639:Bicarbonates / Q000378:metabolism; D001692:Biological Transport; D001794:Blood Pressure / Q000187:drug effects; D002712:Chlorides / Q000378:metabolism; D004285:Dogs; D004976:Ethacrynic Acid / Q000494:pharmacology; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D007678:Kidney Glomerulus / Q000187:drug effects / Q000502:physiology*; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008954:Models, Biological; D011188:Potassium / Q000378:metabolism; D012964:Sodium / Q000378:metabolism
D001639:Bicarbonates; D002712:Chlorides; D012964:Sodium; D004976:Ethacrynic Acid; D000086:Acetazolamide; D011188:Potassium