title: Leukotrienes, but not angiotensin II, are involved in the renal effects elicited by the prolonged cyclooxygenase-2 inhibition when sodium intake is low.
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·d, SC75416), and either a vehicle, an AT1 receptor antagonist (0.4 mg · kg · d, candesartan) or a selective 5-lipooxygenase inhibitor (PF-150, 20 and 60 mg · kg · d). 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.
authors.affiliation: Department of Physiology, School of Medicine, University of Murcia, Murcia, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Salazar
authors.forename: F Javier
authors.initials: FJ
authors.lastname: Salazar
authors.forename: Fara
authors.initials: F
authors.lastname: Saez
authors.forename: Virginia
authors.initials: V
authors.lastname: Reverte
authors.forename: Ben
authors.initials: B
authors.lastname: Zweifel
authors.forename: Dawn
authors.initials: D
authors.lastname: Dufield
authors.forename: Melissa
authors.initials: M
authors.lastname: Radabaugh
authors.forename: Matt
authors.initials: M
authors.lastname: Graneto
authors.forename: Maria T
authors.initials: MT
authors.lastname: Llinas
authors.forename: Jaime L
authors.initials: JL
authors.lastname: Masferrer
mesh_terms: D000804:Angiotensin II / Q000378:metabolism*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D001578:Benzopyrans / Q000494:pharmacology; D001713:Biphenyl Compounds; D051546:Cyclooxygenase 2 / Q000187:drug effects / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D004039:Diet, Sodium-Restricted; D004285:Dogs; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007668:Kidney / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism; D015289:Leukotrienes / Q000378:metabolism*; D016859:Lipoxygenase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D011714:Pyrans / Q000008:administration & dosage / Q000494:pharmacology; D011720:Pyrazoles / Q000008:administration & dosage / Q000494:pharmacology; D012079:Renal Circulation / Q000187:drug effects; D013777:Tetrazoles / Q000494:pharmacology
chemical_list: C584202:4-(3-((3-fluoro-4-(1-methyl-1H-pyrazol-5-yl)phenyl)thio)phenyl)tetrahydro-2H-pyran-4-carboxamide; D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001578:Benzopyrans; D001713:Biphenyl Compounds; D052246:Cyclooxygenase 2 Inhibitors; D015289:Leukotrienes; D016859:Lipoxygenase Inhibitors; D011714:Pyrans; D011720:Pyrazoles; C529433:SC-75416; D013777:Tetrazoles; D000804:Angiotensin II; D051546:Cyclooxygenase 2; C081643:candesartan