Wine polyphenols induce hypotension, and decrease cardiac reactivity and infarct size in rats: involvement of nitric oxide

The effects of short‐term oral administration of red wine polyphenolic compounds (RWPC, 20 mg kg −1 day −1 for 7 days) on haemodynamics, ex vivo cardiac responsiveness and ischaemia–reperfusion injury were investigated in rats. The involvement of nitric oxide (NO) was evaluated using the NO synthase inhibitor, N G ‐nitro‐ L ‐arginine methyl ester ( L ‐NAME, 2 mg kg −1 day −1 for 7 days), at a dose which did not affect blood pressure.Ex vivo reactivity of hearts from RWPC‐treated rats showed lower basal developed pressure, greater heart rate and decreased inotropic responses to either β ‐adrenoceptor or muscarinic receptor stimulation with isoprenaline or carbachol, respectively. RWPC treatment did not modify cardiac expression of endothelial NO synthase or Cu/Zn superoxide dismutase. However, it increased nitrite in the coronary effluent. In ischaemia–reperfusion, RWPC treatment reduced infarct size and oxidative stress, as shown by the myocardial content of the end products of lipid peroxidation, malondialdehyde and 4‐hydroxynonenal, without affecting post‐ischaemic contractile dysfunction. All the observed effects of RWPC were prevented by L ‐NAME treatment. Altogether, these data show that short‐term treatment with RWPC decreases blood pressure and cardiac responsiveness, and protects against post‐ischaemic infarction via decreased oxidative stress. All the above effects of RWPC are sensitive to NO synthase inhibition that implies an involvement of NO‐dependent pathway. This study suggests a basis for the beneficial effects of plant‐derived polyphenols against cardiovascular disease.British Journal of Pharmacology (2004) 142 , 671–678. doi: 10.1038/sj.bjp.0705833