title: Adenosine A1 receptor antagonist blunts urinary potassium excretion, but not renal hemodynamic effects, induced by carbonic anhydrase inhibitor in rats.
abstract: Acetazolamide (AZ) is a carbonic anhydrase inhibitor with diuretic actions at the proximal tubule. Clinical use of AZ is limited, in part, because of the urinary potassium loss and decrease of renal hemodynamic function that accompanies the drug. There is recent interest in A1 adenosine receptor (A1AR) antagonists, a novel class of diuretic agents that do not cause loss of potassium or tubuloglomerular feedback- (TGF) mediated reductions of renal hemodynamics. We tested whether the A1AR antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) could attenuate the adverse effects normally associated with use of AZ. Renal blood flow (RBF) and urine output were measured during two consecutive 40-min periods in anesthetized rats. In the first period, vehicle or DPCPX was infused. DPCPX alone increased urine output and sodium excretion but did not significantly alter potassium output or RBF. In the second period, the initial infusion of vehicle or DPCPX was continued, and either AZ or its vehicle was administered. AZ alone increased urinary excretion of both sodium and potassium and decreased RBF. DPCPX significantly attenuated the AZ-induced increase of potassium excretion by 50% but did not blunt the renal hemodynamic response to AZ. In a separate study, angiotensin II type 1 (AT1) receptor blockade also failed to blunt the renal hemodynamic response to AZ. In summary, A1AR antagonists may be useful diuretic agents alone or in combination with other conventional diuretic agents. The decrease of RBF that occurred in response to carbonic anhydrase inhibition was not attenuated by either A1AR blockade or AT1 receptor blockade and does not seem to be mediated by a TGF-dependent mechanism.
authors.affiliation: Department of Basic Biomedical Sciences, University of South Dakota School of Medicine, Vermillion, 57069, USA.
authors.forename: Xiaosun
authors.initials: X
authors.lastname: Zhou
authors.forename: Curtis K
authors.initials: CK
authors.lastname: Kost
mesh_terms: D000086:Acetazolamide / Q000009:adverse effects*; D058916:Adenosine A1 Receptor Antagonists; D000818:Animals; D002257:Carbonic Anhydrase Inhibitors / Q000009:adverse effects*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007668:Kidney / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism; D008297:Male; D011188:Potassium / Q000652:urine*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects; D012964:Sodium / Q000652:urine; D014970:Xanthines / Q000494:pharmacology*
chemical_list: D058916:Adenosine A1 Receptor Antagonists; D002257:Carbonic Anhydrase Inhibitors; D014970:Xanthines; D012964:Sodium; C051360:1,3-dipropyl-8-cyclopentylxanthine; D000086:Acetazolamide; D011188:Potassium