title: The effects of cyclooxygenase and nitric oxide synthase inhibition on oxidative stress in isolated rat heart.
abstract: Despite the widespread clinical use of cyclooxygenase (COX) inhibitors, dilemmas still exist about potential impact of these drugs on cardiovascular system. The present study was aimed to estimate the effects of different COX inhibitors (meloxicam, acetylsalicylic acid [ASA], and SC-560) on oxidative stress in isolated rat heart, with special focus on L-arginine/NO system. The hearts of male Wistar albino rats (total number n = 96, each group 12 rats, 8 weeks old, body mass 180-200 g) were retrogradely perfused according to the Langendorff technique at gradually increased perfusion pressure (40-120 cmH2O). After control experiments the hearts were perfused with the following drugs: 100 μmol/l ASA (Aspirin), alone or in combination with 30 μmol/l L-NAME, 0.3 μmol/l meloxicam (movalis) with or without 30 μmol/l L-NAME, 3 μmol/l meloxicam (alone or in combination with 30 μmol/l L-NAME), 30 μmol/l L-NAME, and administration of 0.25 μmol/l SC-560. In samples of coronary venous effluent the following oxidative stress markers were measured spectrophotometrically: index of lipid peroxidation (measured as thiobarbituric acid reactive substances [TBARS]), superoxide anion radical release (O2(-)), and hydrogen peroxide (H2O2). While ASA was found to have an adverse influence on redox balance in coronary circulation, and coronary perfusion, meloxicam and SC-560 do not negatively affect the intact model of the heart. Furthermore, all effects were modulated by NOS inhibition. It seems that interaction between COX and L-arginine/NO system truly exists in coronary circulation, and can be one of the possible causes for achieved effects. That means: those effects induced by different inhibitors of COX are modulated by subsequent inhibition of NOS.
authors.affiliation: Department of Physiology, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia.
authors.forename: Nevena
authors.initials: N
authors.lastname: Barudzic
authors.forename: Drenka
authors.initials: D
authors.lastname: Turjacanin-Pantelic
authors.forename: Vladimir
authors.initials: V
authors.lastname: Zivkovic
authors.forename: Dragica
authors.initials: D
authors.lastname: Selakovic
authors.forename: Ivan
authors.initials: I
authors.lastname: Srejovic
authors.forename: Jovana
authors.initials: J
authors.lastname: Joksimovic
authors.forename: Jovana
authors.initials: J
authors.lastname: Jakovljevic
authors.forename: Dragan M
authors.initials: DM
authors.lastname: Djuric
authors.forename: Vladimir Lj
authors.initials: VLj
authors.lastname: Jakovljevic
mesh_terms: D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000378:metabolism; D066298:In Vitro Techniques; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D009206:Myocardium / Q000201:enzymology* / Q000473:pathology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013481:Superoxides / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D016861:Cyclooxygenase Inhibitors; D017392:Thiobarbituric Acid Reactive Substances; D013481:Superoxides; D006861:Hydrogen Peroxide; D019001:Nitric Oxide Synthase; D001241:Aspirin; D019331:NG-Nitroarginine Methyl Ester