Antioxidative and myocardial protective effects of L-arginine in oxygen radical-induced injury of isolated perfused rat hearts.
Oxygen-derived free radicals and oxidants (reactive oxygen intermediates, ROI) have been implicated in cardiovascular diseases. The protective role of nitric oxide (NO) against ROI-mediated tissue injury is not resolved. We tested the effects of exogenous NO, L- and D-arginine and a NO synthase inhibitor on electrolysis-induced cardiac injury and the generation of ROI by electrolysis. Superoxide dismutase (SOD) and catalase were used for comparison. Hearts ( n=7) from male rats (350+/-30 g) were perfused in vitro at 10 ml min(-1) g(-1), ROI generated by electrolysis of the perfusion medium (15 mA, 10 s), and cardiac function and the level of isoluminol-derived chemiluminescence in electrolysed perfusion medium documented for 15 min ( n=4). The ROI-induced maximal reduction of left ventricular developed pressure to 55+/-5% of baseline, and a 2.2+/-0.1-fold rise in coronary perfusion pressure 3 min after electrolysis, were prevented by SOD (50 U ml(-1)), catalase (100 U ml(-1)), S-nitroso- N-acetyl- D,L-penicillamine (SNAP, 100 nmol l(-1)); L-arginine (1 mmol l(-1)), N(G)-nitro- L-arginine (L-NNA, 200 micromol l(-1)) or D-arginine (1 mmol l(-1)). The effect of L-arginine was concentration dependent. In all cases, the beneficial effects were closely matched by a near-total reduction of ROI in the perfusion medium.We conclude that, besides mimicking or enhancing NO activity, L-arginine and donor-derived exogenous NO are cardioprotective by reducing ROI-mediated tissue injury. The protective effect of L-NNA and D-arginine implies that the protection results from a direct chemical interaction between the drug and the oxidizing species.
Suessenbacher
Astrid
A
Institut für Pharmakologie und Toxikologie, Karl-Franzens-Universität Graz, Universitätsplatz 2, 8010 Graz, Austria.
Lass
Achim
A
Mayer
Bernd
B
Brunner
Friedrich
F
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001120:Arginine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004572:Electrolysis; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D008163:Luminescent Measurements; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000139:chemically induced / Q000517:prevention & control*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000032:analysis / Q000633:toxicity*; D018487:Ventricular Dysfunction, Left / Q000139:chemically induced
D000975:Antioxidants; D020030:Nitric Oxide Donors; D017382:Reactive Oxygen Species; D001120:Arginine; D019001:Nitric Oxide Synthase