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Several reports suggest that consumption of red wine is associated with a lower risk of stroke. We investigated the chronic effect of red wine polyphenols (RWP) on the functional and structural characteristics of cerebral arterioles in chronic hypertension, which is an important risk factor of stroke. Spontaneous hypertensive rats (SHR) were treated with RWP extract (100 mg/kg/day in drinking water) for 10 weeks. We measured the effect of agonist- and hypotension-induced changes in internal diameter of cerebral arterioles using an open cranial window technique. Wall mechanical parameters were determined in deactivated cerebral arterioles. The activity of antioxidant enzymes in plasma was determined. Adenosine diphosphate-induced vasodilatation was decreased by 48% in SHR and normalized in SHR treated with RWP. RWP had no effect on hypotension-induced dilatation. RWP decreased the wall thickness/external diameter ratio by 13% and significantly shifted the stress-strain relationship of the arteriole wall to the left. There was a decrease in glutathione-S-transferase and glutathione peroxidase after treatment of RWP in SHR. In summary, chronic oral administration of RWP to SHR improved endothelium-dependent dilatation, normalized wall stress and diameter, and altered the systemic antioxidant state. These effects of RWP could be useful in the prevention of stroke in hypertensive patients.

We studied the effect of age on the response of aortic rings to injury produced by three days' incubation, and the mechanism of this response. Five-mm rings of the thoracic aorta isolated from Wistar rats were incubated or not in culture medium. Isometric contraction evoked by agonists (norepinephrine or serotonin) or high [K(+)](e) was determined in the presence and absence of endothelium. Experiments were repeated in the presence of propranolol (0.3 microM), polymixin B (36 microM), pyrrolidine dithiocarbamate (50 microM) or glutathione (3 mM). Inductible NO-synthase and cyclo-oxygenase-2 mRNA were determined by real-time PCR, and glutathione-related enzymes and catalase activity by spectrophotometry. Incubation reduced the isometric contraction evoked by agonists but not by high [K(+)](e). The reduction in agonist-evoked contraction was greater in rings from adult (norepinephrine Emax-80%) than in young (-40%) rats. The removal of the endothelium had no effect. The reduction in norepinephrine-evoked contraction was not due to endotoxin contamination, beta-adrenoceptor-mediated dilation or any change in ring structure (no fibrosis or edema). Inductible NO-synthase (but not cyclo-oxygenase-2) mRNA increased on incubation. N(G)-nitro-L-arginine methyl ester partially restored contractility in rings from adult animals, further addition of an anti-oxidant restored norepinephrine-evoked contraction. Catalase fell with age and glutathione reductase increased upon incubation in rings from young donors only. In conclusion, incubation of the aorta produces a specific reduction in agonist-evoked contraction that involves induction of smooth muscle cell oxidative stress and iNOS. The reaction is greater in rings from older animals.