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

The carbonic anhydrase inhibitor acetazolamide (ACZ) inhibits the abso lute rate of proximal reabsorption (APR), causes a reduction in glomer ular filtration rate (GFR), and activates the tubuloglomerular feedbac k mechanism (TGF) resulting in afferent vasoconstriction. The quantita tive importance of the afferent vasoconstriction for the reduced GFR w as tested by addition of a vasodilator during continuous infusion of A CZ. Dopamine caused an increase in renal blood flow (RBF) to pre-ACZ l evels. Glomerular capillary pressure (P-gc) and proximal tubular press ure (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 f low almost doubled. GFR was only modestly reversed (pre-ACZ/ACZ/ACZ dopamine: 100/77/83%). It is concluded that relieving the afferent vas oconstriction seen after carbonic anhydrase inhibition fails to restor e GFR to its control value. This is due to the high flow resistance in the distal nephron segments during the increased tubular flow rates s een after ACZ. The high distal flow resistance causes a parallel chang e in P-gc and P-prox and thus leaves Delta P nearly unchanged. The pre sent study highlights the importance of the distal flow resistance in determining Delta P and therefore GFR during conditions where tubular flow rate is increased.