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1. The effects of ethyl alcohol and wine (red and white) on haemostatic parameters and experimental thrombosis were studied in rats; NO was evaluated as a possible mediator of these effects. 2. We found that red wine (12% alcohol) supplementation (8.4 +/- 0.4 ml d-1 in drinking water, for 10 days) induced a marked prolongation of 'template' bleeding time (BT) (258 +/- 13 vs 132 +/- 13 s in controls; P < 0.001), a decrease in platelet adhesion to fibrillar collagen (11.6 +/- 1.0 vs 32.2 +/- 1.3%; P < 0.01) and a reduction in thrombus weight (1.45 +/- 0.33 vs 3.27 +/- 0.39 mg; P < 0.01). 3. Alcohol-free red wine showed an effect similar to red wine. In contrast, neither ethyl alcohol (12%) nor white wine (12% alcohol) affected these systems. 4. All these effects were also observed after red wine i.v. injection (1 ml kg-1 of 1:4 dilution) 15 min before the experiments. 5. The effects of red wine were prevented by the NO inhibitor, N omega nitro-L-arginine-methyl ester (L-NAME). L-arginine, not D-arginine, reversed the effect of L-NAME on red wine infusion. 6. Red wine injection induced a 3 fold increase in total radical-trapping antioxidant parameter values of rat plasma with respect to controls, while white wine and alcohol did not show any effect. 7. Our study provides evidence that red wine modulates primary haemostasis and prevents experimental thrombosis in rats, independently of its alcohol content, by a NO-mediated mechanism.

The present study was aimed at clarifying the interaction between red blood cell trauma and bleeding observed in some clinical conditions. Acute hemolysis provoked by distilled water injection was followed by a significant prolongation of the "template" bleeding time in rats. Comparable effects were observed after injection of an isotonic lysate of washed red blood cells. N omega-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide (NO) formation from L-arginine, normalized bleeding time when given to rats before hemolysis induction. The occurrence of hemolysis decreased ex vivo platelet adhesion to collagen without affecting platelet aggregation and induced a transient drop in blood pressure, the latter occurring during the first minute after injection. L-NAME pretreatment increased ex vivo platelet adhesion but did not affect either platelet aggregation or fall in blood pressure. All the effects of L-NAME were blunted by treating the animals with the NO precursor L-arginine but not D-arginine. Incubation of the erythrocyte lysate with apyrase prevented the prolongation of bleeding time induced by the hemolysate. Moreover, ADP administration, at doses that did not increase hemoglobin levels, induced effects similar to those observed after hemolysis (on template bleeding time and ex vivo platelet adhesion), which were also reversed by L-NAME and restored by L-arginine. ADP is abundantly released from (hemo)lysed red blood cells and is known to stimulate release of NO, a potent vasodilator and inhibitor of platelet adhesion. ADP-dependent NO release could be responsible for bleeding time prolongation, due to abnormalities in platelet-vessel wall interaction, during acute hemolysis. Lysis of white blood cells may also contribute to prolongation of bleeding time. Because ADP could not be detected in these cells, we postulate that other mechanisms also can be involved in bleeding time prolongation after blood cell activation in vivo.