ON DETERMINANTS OF GLOMERULAR-FILTRATION RATE AFTER INHIBITION OF PROXIMAL TUBULAR REABSORPTION

The carbonic anhydrase inhibitor acetazolamide (ACZ) inhibits the absolute rate of proximal reabsorption (APR), causes a reduction in glomerular filtration rate (GFR), and activates the tubuloglomerular feedback mechanism (TGF) resulting in afferent vasoconstriction. The quantitative importance of the afferent vasoconstriction for the reduced GFR was tested by addition of a vasodilator during continuous infusion of ACZ. Dopamine caused an increase in renal blood flow (RBF) to pre-ACZ levels. Glomerular capillary pressure (P-gc) and proximal tubular pressure (P-prox) increased in parallel (by 3.1 and 3.0 mmHg, respectively) leaving pressure gradient (Delta P) unchanged. APR, as estimated from the clearances of Cr-51-EDTA and lithium, remained unchanged. Urine flow almost doubled. GFR was only modestly reversed (pre-ACZ/ACZ/ACZ + dopamine: 100/77/83%). It is concluded that relieving the afferent vasoconstriction seen after carbonic anhydrase inhibition fails to restore GFR to its control value. This is due to the high flow resistance in the distal nephron segments during the increased tubular flow rates seen after ACZ. The high distal flow resistance causes a parallel change in P-gc and P-prox and thus leaves Delta P nearly unchanged. The present study highlights the importance of the distal flow resistance in determining Delta P and therefore GFR during conditions where tubular flow rate is increased.