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

1 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. 2 Ex vivo reactivity of hearts from RWPC-treated rats showed lower basal developed pressure, greater heart rate and decreased inotropic responses to either beta-adrenoceptor or muscarinic receptor stimulation with isoprenaline or carbachol, respectively. 3 RWPC treatment did not modify cardiac expression of endothelial NO synthase or Cu/Zn superoxide dismutase. However, it increased nitrite in the coronary effluent. 4 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. 5 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).