Skip Navigation LinksHome > April 2013 - Volume 61 - Issue 4 > Leukotrienes, But Not Angiotensin II, Are Involved in the Re...
Journal of Cardiovascular Pharmacology:
doi: 10.1097/FJC.0b013e31828399ae
Original Article

Leukotrienes, But Not Angiotensin II, Are Involved in the Renal Effects Elicited by the Prolonged Cyclooxygenase-2 Inhibition When Sodium Intake Is Low

Salazar, Francisco PhD*; Salazar, F. Javier PhD*; Saez, Fara PhD*; Reverte, Virginia PhD*; Zweifel, Ben; Dufield, Dawn PhD; Radabaugh, Melissa; Graneto, Matt PhD; Llinas, Maria T. PhD*; Masferrer, Jaime L. PhD

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Abstract

Abstract: It is known that cyclooxygenase-2 (COX-2) inhibition elicits significant renal hemodynamics alterations when sodium intake is low. However, the mechanisms involved in these renal changes are not well known. Our objective was to evaluate the role of angiotensin II and 5-lipooxygenase-derived metabolites in the renal effects induced by prolonged COX-2 inhibition when sodium intake is low. Conscious dogs were treated during 7 days with a COX-2 inhibitor (1 mg·kg−1·d−1, SC75416), and either a vehicle, an AT1 receptor antagonist (0.4 mg·kg−1·d−1, candesartan) or a selective 5-lipooxygenase inhibitor (PF-150, 20 and 60 mg·kg−1·d−1). The administration of SC75416 alone induced significant changes in renal blood flow (219 ± 14 to 160 ± 10 mL/min), glomerular filtration rate (51 ± 2 to 42 ± 3 mL/min), and plasma potassium (pK) (4.3 ± 0.1 to 4.6 ± 0.1 mEq/L). Similar decrements in renal blood flow (27%) and glomerular filtration rate (20%) and a similar increment in pK (7%) were found when SC75416 was administered in candesartan-pretreated dogs. However, SC75416 administration did not elicit significant changes in renal hemodynamics and pK in dogs pretreated with each dose of PF-150. Our data suggest that leukotrienes but not angiotensin II are involved in the renal effects induced by COX-2 inhibition when sodium intake is low.

© 2013 Lippincott Williams & Wilkins, Inc.

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