title: On determinants of glomerular filtration rate after inhibition of proximal tubular reabsorption.
abstract: 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 (Pgc) and proximal tubular pressure (Pprox) increased in parallel (by 3.1 and 3.0 mmHg, respectively) leaving pressure gradient (delta P) unchanged. APR, as estimated from the clearances of 51Cr-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 Pgc and Pprox 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.
authors.affiliation: Department of Medical Physiology, Panum Institute, University of Copenhagen, Denmark.
authors.forename: P P
authors.initials: PP
authors.lastname: Leyssac
authors.forename: F M
authors.initials: FM
authors.lastname: Karlsen
authors.forename: N H
authors.initials: NH
authors.lastname: Holstein-Rathlou
authors.forename: O
authors.initials: O
authors.lastname: Skøtt
mesh_terms: D000042:Absorption; D000086:Acetazolamide / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002196:Capillaries / Q000187:drug effects / Q000502:physiology; D004298:Dopamine / Q000494:pharmacology*; D004492:Edetic Acid / Q000493:pharmacokinetics; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006874:Hydrostatic Pressure; D007678:Kidney Glomerulus / Q000098:blood supply; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000502:physiology*; D008094:Lithium / Q000493:pharmacokinetics; D008297:Male; D008657:Metabolic Clearance Rate; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D008094:Lithium; D004492:Edetic Acid; D000086:Acetazolamide; D004298:Dopamine