期刊
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
卷 365, 期 4, 页码 269-276出版社
SPRINGER
DOI: 10.1007/s00210-001-0523-9
关键词
free radical scavenging; L-arginine; superoxide dismutase; rat heart; contractile function; coronary circulation; cardioprotection; chemiluminescence
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 mumol 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.
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