A B S T R A C T Maintenance of chronic metabolic alkalosis might occur by a reduction in glomerular filtration rate (GFR) without increased bicarbonate reabsorption or, alternatively, by augmentation of bicarbonate reabsorption with a normal GFR. To differentiate these possibilities, free-flow micropuncture was performed in alkalotic Munich-Wistar rats with a glomerular ultrafiltrate total CO2 concentration of 46.5±0.9 mM (vs. 27.7±0.9 mM in controls). Alkalotic animals had a markedly reduced single nephron GFR compared with controls (27.4±1.5 vs. 51.6±1.6 nl/min) and consequently unchanged filtered load of bicarbonate. Absolute proximal bicarbonate reabsorption in alkalotic animals was similar to controls (981±49 vs. 1,081±57 pmol/min), despite a higher luminal bicarbonate concentration, contracted extracellular volume, and potassium depletion. When single nephron GFR during alkalosis was increased toward normal by isohydric volume expansion or in another group by isotonic bicarbonate loading, absolute proximal bicarbonate reabsorption was not substantially augmented and bicarbonaturia developed. To confirm that a fall in GFR occurs during metabolic alkalosis, additional clearance studies were performed. Awake rats were studied before and after induction of metabolic alkalosis associated with varying amounts of potassium Portions of this work were presented at the National Meet-
These studies examined regulation of superficial proximal convoluted tubule (PCIT) transport as a function of length. When single nephron glomerular filtration rate (SNGFR) increased from 28.7±0.7 nl/min in hydropenia to 41.5±0.4 nl/min in euvolemia, bicarbonate, chloride, and water reabsorption in the early (1st mm) PCI' increased proportionally: from 354±21 peaJ mm * min, 206±55 peq/mni * min, and 5.9±0.4 nl/mm * min to 520±12 peq/mm. min, 585±21 peq/mm * min, and 10.1 ±0.4 nl/ mm* min, respectively. These high transport rates did not increase further, however, when SNGFR went to 51.2±0.7 or 50.7±0.6 nl/min after atrial natriuretic factor or glucagon administration. Anion and water transport rates in the late PCI were lower and exhibited less flow dependence. During chronic metabolic alkalosis, acidification was inhibited in the late but not early PCT. In conclusion, the early PCI is distinguished from the late PCI by having high-capacity, flow-responsive but saturable, anion-and water-reabsorptive processes relatively unaffected by alkalemia.
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