Postischemic Recovery and Oxidative Stress Are Independent of Nitric-Oxide Synthases Modulation in Isolated Rat Heart

• Published in: The Journal of pharmacology and experimental therapeutics 2002-10, Vol.303 (1), p.149-157
• Main Authors: Vergely, Catherine, Perrin-Sarrado, Caroline, Clermont, Gaëlle, Rochette, Luc
• Format: Article
• Language: English
• Subjects: Animals; Arginine - pharmacology; Blood Pressure - drug effects; Blood Pressure - physiology; Coronary Circulation - drug effects; Coronary Circulation - physiology; Heart - drug effects; Heart - physiology; Heart - physiopathology; Heart Rate - drug effects; Heart Rate - physiology; In Vitro Techniques; Kinetics; Myocardial Ischemia - physiopathology; Myocardial Reperfusion; Myocardium - enzymology; NG-Nitroarginine Methyl Ester - pharmacology; Nitric Oxide Synthase - metabolism; Oxidative Stress - physiology; Perfusion - methods; Rats; Superoxides - metabolism; Ventricular Function, Left - drug effects; Ventricular Function, Left - physiology
• ISSN: 0022-3565; 1521-0103
• DOI: 10.1124/jpet.102.036871

During myocardial ischemia and reperfusion, nitric oxide ( ⋅ NO) was shown to exert either beneficial or detrimental effects. Uncoupled ⋅ NO synthases (NOS) can generate superoxide anion under suboptimal concentrations of substrate and cofactors. The aim of our study was to investigate the role of NOS modulation on 1) the evolution of functional parameters and 2) the amount of free radicals released during an ischemia-reperfusion sequence. Isolated perfused rat hearts underwent 30 min of total ischemia, followed by 30 min of reperfusion in the presence of N G -nitro- d - or l -arginine methyl ester (NAME, 100 μM) or of d - or l -arginine (3 mM). Functional parameters were recorded and coronary effluents were analyzed with electron spin resonance to identify and quantify the amount of α-phenyl- N - tert- butylnitrone spin adducts produced during reperfusion. The antioxidant capacities of the compounds were determined with the oxygen radical absorbance capacity test. l -NAME-treated hearts showed a reduction of coronary flow and contractile performance, although neither l -NAME nor l -arginine improved the recovery of coronary flow, left end diastolic ventricular pressure, rate pressure product, and duration of reperfusion arrhythmia, compared with their d -specific enantiomers. A large and long-lasting release of alkyl/alkoxyl radicals was detected upon reperfusion, but no differences of free radical release were observed between d - and l -NAME or d - and l -arginine treatment. These results may indicate that, in our experimental conditions, cardiac NOS might not be a major factor implicated in the oxidative burst that follows a global myocardial ischemia.