Antioxidative and myocardial protective effects of L-arginine in oxygen radical-induced injury of isolated perfused rat hearts

Abstract.

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 µmol 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.