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 x 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 x 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.