Resveratrol provides late-phase cardioprotection by means of a nitric oxide- and adenosine-mediated mechanism.
We used two experimental models to prove that resveratrol (trans-3,4',5-trihydroxystilbene) reduces cardiac ischemic-reperfusion injury by means of a nitric oxide- and adenosine-dependent mechanism. (1). ACUTE EX VIVO: resveratrol (10 microM, 10 min) infusion in Langendorff-perfused normoxic rat hearts significantly increased adenosine release and coronary flow compared with baseline. After 30-min low-flow ischemia, vasodilation, still present at reperfusion, was completely abolished by resveratrol plus adenosine antagonist 8-(p-sulfophenyl)theophylline (SPT, 50 microM) administration. (2). CHRONIC IN VIVO: rats received tap water containing 25 mg/l resveratrol for 15 days or normal water. Twenty-four hours after, their hearts were Langendorff-perfused and submitted to 60-min low-flow ischemia and reperfusion. The resveratrol-treated hearts showed better functional recovery at reperfusion and significant vasodilation, but no variation in high-energy phosphates (31P Nuclear Magnetic Resonance). N(G)-nitro-L-arginine methyl ester (L-NAME, 30 microM), a nonselective nitric oxide synthase inhibitor, or SPT (50 microM) administered for 10 min prior to the low-flow ischemia cancelled the effects. This suggests that long-term moderate resveratrol consumption could play an important role in late cardioprotective effects.
Bradamante
Silvia
S
CNR-Istituto Scienze e Tecnologie Molecolari, University of Milan, Via Golgi 19, I-20133 Milan, Italy. brada@icil64.cilea.it
Barenghi
Livia
L
Piccinini
Franco
F
Bertelli
Alberto A E
AA
De Jonge
Robert
R
Beemster
Patricia
P
De Jong
Jan Willem
JW
D000241:Adenosine / Q000378:metabolism*; D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology; D003326:Coronary Circulation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006321:Heart / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D017202:Myocardial Ischemia / Q000150:complications / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000209:etiology / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D013806:Theophylline / Q000031:analogs & derivatives* / Q000494:pharmacology; D013997:Time Factors; D014665:Vasodilator Agents / Q000494:pharmacology*
D002316:Cardiotonic Agents; D004791:Enzyme Inhibitors; D058915:Purinergic P1 Receptor Antagonists; D013267:Stilbenes; D014665:Vasodilator Agents; D009569:Nitric Oxide; C031433:8-(4-sulfophenyl)theophylline; D013806:Theophylline; D019001:Nitric Oxide Synthase; D000241:Adenosine; D000077185:Resveratrol; D019331:NG-Nitroarginine Methyl Ester