Procyanidins from Vitis vinifera seeds display cardioprotection in an experimental model of ischemia-reperfusion damage.
Since the early 1970s, increasing evidence has suggested that the consumption of moderate amounts of alcohol is inversely correlated with mortality from myocardial infarction. There is also some evidence that the protective effects of wine might be more pronounced than those of other alcoholic beverages. These observations prompted us to investigate the cardioprotective activity of Vitis vinifera seeds in experimental ischemia-reperfusion injury. An isolated rabbit heart preparation paced electrically was used to evaluate the effects of a highly purified, high molecular weight fraction of oligomeric procyanidins isolated from Vitis vinifera seeds on myocardial reperfusion injury after 40 min of low-flow (1 ml/min) ischemia. Infusion of the heart with 100 or 200 microg/ml procyanidins dose-dependently reduced left ventricular end-diastolic pressure during ischemia, decreased coronary perfusion pressure, improved cardiac mechanical performance upon reperfusion, increased the release of 6-Keto-prostaglandin F1alpha into the perfusate in both the preischemic and the reperfusion periods and suppressed rhythm irregularity. Procyanidins dose-dependently relaxed human internal mammary aortic (IMA) rings (with intact endothelium) precontracted with norepinephrine. This effect was completely abolished in IMA-rings without functional endothelium or when this vascular tissue was pretreated with nitric oxide synthase inhibitor (NG-monomethyl-L-arginine) or with guanylate cyclase inhibitor (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one). In conclusion, these results indicate that procyanidins could be of therapeutical potential in cardiovascular diseases. However, further investigations are required for a better definition of the mode of action of these oligomers.
Berti
F
F
Department of Pharmacology, Chemotherapy and Medical Toxicology, University of Milan, Italy. ferruccio.berti@unimi.it
Manfredi
B
B
Mantegazza
P
P
Rossoni
G
G
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D044946:Biflavonoids / Q000008:administration & dosage / Q000494:pharmacology*; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002392:Catechin / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D066298:In Vitro Techniques; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D010069:Oxadiazoles / Q000494:pharmacology; D044945:Proanthocyanidins / Q000008:administration & dosage / Q000494:pharmacology*; D011810:Quinoxalines / Q000494:pharmacology; D011817:Rabbits; D012639:Seeds / Q000737:chemistry; D014665:Vasodilator Agents / Q000494:pharmacology*; D027843:Vitis / Q000737:chemistry*
C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D044946:Biflavonoids; D002316:Cardiotonic Agents; D010069:Oxadiazoles; D044945:Proanthocyanidins; D011810:Quinoxalines; D014665:Vasodilator Agents; D019335:Nitroarginine; C017674:procyanidin; D015121:6-Ketoprostaglandin F1 alpha; D002392:Catechin; D019001:Nitric Oxide Synthase; D006162:Guanylate Cyclase; D009638:Norepinephrine