Low to moderate consumption of red wine reportedly has a relatively greater benefit than other alcoholic beverages in the prevention of atherosclerosis and coronary heart disease (CHD). This beneficial effect is increasingly attributed to the polyphenol resveratrol, present in red wine. In the present study, we investigated the effects of resveratrol and red wine on aggregation of platelets isolated from healthy, normotensive male volunteers and in rabbits with experimental hypercholesterolemia. Platelet aggregation rate (PAR) was measured using Born's method. The results showed that aggregation of platelets from healthy subjects induced in vitro by collagen (5 µg/ml), thrombin (0.33 units/ml), and ADP (4 µM) was significantly inhibited by 10-1000 µM resveratrol, in a concentration-dependent manner. Hypercholesterolemic rabbits showed enhanced ADP-induced platelet aggregation; the average PAR increased from 39.5±5.9% in normal animals to 61.0±7.0% in the high-cholesterol fed group (n=8, p<0.001). Resveratrol (4 mg/kg/day) inhibited ADP-induced platelet aggregation in vivo by maintaining the PAR at 35.7±6.3% (vs. 39.5±5.9% for control rabbits, n=8, p=0.228), but had no effect on serum lipid levels. Similarly platelet aggregation in hypercholesterolemic rabbits was also inhibited when animals received intragastrically Chinese red wine (with or without alcohol, 4 ml/kg/day). These results suggest that resveratrol can inhibit platelet aggregation both in vitro and in vivo, which conceivably could be one of the mechanisms by which this red wine polyphenol exerts its cardioprotective effects.

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Lidocaine has been reported to inhibit nitric oxide (NO) production in activated murine macrophages, but the role of inducible NO synthase (iNOS) in lidocaine-induced inhibition of NO has not been explored. In addition, type-2 cationic amino acid transporter (CAT-2) and guanosine triphosphate cyclohydrolase I (GTPCH) also regulate iNOS activity. The effects of lidocaine on CAT-2 and GTPCH are unknown. To explore further these effects, confluent immortalized murine macrophages (RAW264.7 cells) were incubated with lipopolysaccharide (LPS) or in combination with lidocaine (5, 50, or 500 microM) for 18 h before harvesting. We also used tetrodotoxin (TTX) and veratridine to elucidate the possible role of voltage-sensitive Na+ channel. Our data demonstrated that LPS significantly upregulated transcription of iNOS and CAT-2 but not GTPCH in stimulated macrophages. In a dose-dependent manner, lidocaine significantly attenuated the LPS-induced upregulation of iNOS and CAT-2. Conversely, lidocaine significantly increased GTPCH transcription in LPS-stimulated macrophages. The effects of TTX on iNOS, CAT-2, and GTPCH expression were comparable to those of lidocaine. In addition, veratridine significantly attenuated the effects of lidocaine and TTX. We therefore concluded that lidocaine significantly inhibits iNOS and CAT-2 and, in turn, enhances GTPCH transcription in LPS-stimulated macrophages via a mechanism that possibly involves the voltage-sensitive Na+ channel.

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