title: Mechanism of acetazolamide-induced rise in renal vascular resistance assessed in the dog whole kidney.
abstract: The reduction in renal blood flow (RBF) and glomerular filtration rate (GFR) observed after the administration of the carbonic anhydrase inhibitors acetazolamide and benzolamide had been explained as due to activation of the tubuloglomerular feedback mechanism. If correct, pharmacologic blockade of this pathway should prevent the development of renal vasoconstriction with the carbonic anhydrase inhibitors. Thus, the current study evaluates in the dog whole kidney the effect of acetazolamide (20 mg/kg body weight) in the presence or absence of furosemide (5 mg/kg body weight), a drug which blocks the tubuloglomerular feedback. Acetazolamide resulted in a large increase in urinary bicarbonate excretion accompanied by a significant reduction in GFR (16%) and RBF (18%). By contrast with the effects of acetazolamide, furosemide did not alter GFR and increased RBF. In addition, the loop diuretic induced a large chloruresis without changes in urinary bicarbonate excretion. The infusion of acetazolamide in furosemide-treated dogs resulted in a significant increment in renal bicarbonate excretion and in a significant reduction in the levels of both GFR (28%) and RBF (13%). Therefore, furosemide pretreatment did not block the effects of acetazolamide on renal hemodynamic parameters. Consequently, the acetazolamide-induced reduction in both GFR and RBF cannot be accounted for by changes in chloride levels in the juxtaglomerular region due to enhanced salt transport in the macula densa/distal nephron. The increased renal vascular resistance observed with acetazolamide might occur by either a direct effect of this agent on the renal circulation or as a result of changes in intrarenal pressure secondary to the inhibition of proximal fluid reabsorption.
authors.affiliation: Renal Section, Hospital de Clinicas, Universidad de Buenos Aires, Argentina.
authors.forename: N L
authors.initials: NL
authors.lastname: Yeyati
authors.forename: G A
authors.initials: GA
authors.lastname: Altenberg
authors.forename: H J
authors.initials: HJ
authors.lastname: Adrogué
mesh_terms: D000086:Acetazolamide / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D005665:Furosemide / Q000008:administration & dosage / Q000494:pharmacology; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007668:Kidney / Q000187:drug effects; D012079:Renal Circulation / Q000187:drug effects*; D014655:Vascular Resistance / Q000187:drug effects*
chemical_list: D005665:Furosemide; D000086:Acetazolamide