Berti F, Manfredi B, Mantegazza P, Rossoni G
Department of Pharmacology, Chemotherapy and Medical Toxicology, University of Milan, Italy.
Drugs Exp Clin Res. 2003;29(5-6):207-16.
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.
自20世纪70年代初以来，越来越多的证据表明，适量饮酒与心肌梗死死亡率呈负相关。也有一些证据表明，葡萄酒的保护作用可能比其他酒精饮料更为显著。这些观察结果促使我们研究葡萄种子在实验性缺血再灌注损伤中的心脏保护活性。采用电起搏的离体兔心标本，评估从葡萄种子中分离出的高纯度、高分子量低聚原花青素组分对低流量（1毫升/分钟）缺血40分钟后心肌再灌注损伤的影响。向心脏输注100或200微克/毫升原花青素可剂量依赖性地降低缺血期间的左心室舒张末期压力，降低冠状动脉灌注压，改善再灌注时的心脏机械性能，增加缺血前期和再灌注期灌注液中6-酮-前列腺素F1α的释放，并抑制节律不规则。原花青素剂量依赖性地舒张用去甲肾上腺素预收缩的人乳内主动脉（IMA）环（内皮完整）。在无功能内皮的IMA环中，或当该血管组织用一氧化氮合酶抑制剂（NG-单甲基-L-精氨酸）或鸟苷酸环化酶抑制剂（1H-[1,2,4]恶二唑并[4,3-a]喹喔啉-1-酮）预处理时，这种作用完全消失。总之，这些结果表明原花青素在心血管疾病中可能具有治疗潜力。然而，需要进一步研究以更好地确定这些低聚物的作用方式。
