학술논문
The effects of cyclooxygenase and nitric oxide synthase inhibition on oxidative stress in isolated rat heart
Document Type
Academic Journal
Author
Source
Molecular and Cellular Biochemistry. September 1, 2013, Vol. 381 Issue 1-2, p301, 11 p.
Subject
Language
English
ISSN
0300-8177
Abstract
Introduction Non-steroid anti-inflammatory drugs are primarily used in the treatment of acute and chronic inflammation [1] usually as analgesics, anti-inflammatory drugs, and antipyretics [2, 3]. The mechanism of these drugs [...]
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 cm[H.sub.2]O). 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/I 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 ([O.sub.2.sup.-]), and hydrogen peroxide ([H.sub.2][O.sub.2]). 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. Keywords COX inhibitors * Cardiac function * Oxidative stress Isolated rat heart
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 cm[H.sub.2]O). 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/I 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 ([O.sub.2.sup.-]), and hydrogen peroxide ([H.sub.2][O.sub.2]). 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. Keywords COX inhibitors * Cardiac function * Oxidative stress Isolated rat heart