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.
Ralay Ranaivo
Hantamalala
H
Pharmacologie et Physico-Chimie des Interactions Cellulaires et Moleculaires, Universite Louis Pasteur de Strasbourg, UMR CNRS 7034, Faculte de Pharmacie, 67401 Illkirch, France.
Diebolt
Myriam
M
Andriantsitohaina
Ramaroson
R
D000284:Administration, Oral; D000447:Aldehydes / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D015153:Blotting, Western / Q000379:methods; D002217:Carbachol / Q000037:antagonists & inhibitors / Q000494:pharmacology; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005419:Flavonoids / Q000032:analysis* / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D005602:France; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006352:Heart Ventricles / Q000737:chemistry / Q000187:drug effects; D007022:Hypotension / Q000139:chemically induced* / Q000517:prevention & control; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008315:Malondialdehyde / Q000737:chemistry / Q000378:metabolism; D009203:Myocardial Infarction / Q000175:diagnosis / Q000188:drug therapy* / Q000517:prevention & control; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000032:analysis / Q000378:metabolism*; D009573:Nitrites / Q000032:analysis / Q000378:metabolism; D010636:Phenols / Q000032:analysis* / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D059808:Polyphenols; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000175:diagnosis / Q000188:drug therapy / Q000517:prevention & control; D013997:Time Factors; D016276:Ventricular Function; D017725:Ventricular Pressure / Q000187:drug effects / Q000502:physiology; D014920:Wine / Q000032:analysis*
D000447:Aldehydes; D005419:Flavonoids; D009573:Nitrites; D010636:Phenols; D059808:Polyphenols; D009569:Nitric Oxide; D008315:Malondialdehyde; D002217:Carbachol; C027576:4-hydroxy-2-nonenal; D007545:Isoproterenol; D019331:NG-Nitroarginine Methyl Ester