Substrate utilization by the distal nephron in dogs with chronic metabolic acidosis: studies with ethacrynic acid.
Glutamine and lactate oxidations provide the bulk of ATP required for sodium reabsorption in the dog kidney during chronic metabolic acidosis. Indirect evidence has suggested that glutamine is oxidized in the proximal convoluted tubule; if this is true, lactate should be the major fuel of the more distal nephron sites. The purpose of these experiments was to determine which substrates were metabolized by the acidotic dog kidney when a significant proportion of sodium chloride reabsorption was inhibited in the thick ascending limb of the loop of Henle. Ethacrynic acid, a loop diuretic, caused the fractional excretion of sodium to increase from 1 to 34%. The glomerular filtration rate declined somewhat, but there was no significant change in the renal blood flow rate. Renal oxygen consumption declined in conjunction with the natriuresis. However, when the data were examined at a constant filtered load of sodium (a constant rate of ATP turnover), there was no reduction in glutamine uptake or glutamine conversion to ATP in the presence of this natriuretic agent. The major change observed concerned lactate metabolism, in the presence of ethacrynic acid, there was no longer a significant rate of lactate extraction. These data are best explained by assuming that glutamine is the fuel of the proximal convoluted tubule of the acidotic dog kidney, whereas lactate oxidation occurs principally in the nephron sites where sodium reabsorption was inhibited by ethacrynic acid.
D000138:Acidosis / Q000097:blood / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002245:Carbon Dioxide / Q000097:blood; D004285:Dogs; D004976:Ethacrynic Acid / Q000494:pharmacology*; D005260:Female; D006863:Hydrogen-Ion Concentration; D008297:Male; D009399:Nephrons / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects; D012964:Sodium / Q000378:metabolism
D002245:Carbon Dioxide; D000255:Adenosine Triphosphate; D012964:Sodium; D004976:Ethacrynic Acid