de Moura Roberto Soares, Miranda Daniel Z, Pinto Ana Cláudia A, Sicca Raquel F, Souza Marcelo A V, Rubenich Lorna M S, Carvalho Lenize C R M, Rangel Bruno M, Tano Tania, Madeira Socorro V F, Resende Angela C
Department of Pharmacology, State University of Rio de Janeiro, Rio de Janeiro, Brazil.
J Cardiovasc Pharmacol. 2004 Sep;44(3):302-9. doi: 10.1097/01.fjc.0000133060.10597.3c.
The mechanisms involved in the cardioprotector effect of red wine have not yet been completely elucidated but probably an endothelium-dependent vasodilator action may play a significant role in this effect. Experiments were undertaken to determine whether a Brazilian red wine (BRW) induces vasodilation in the mesenteric vascular bed (MVB) and an antihypertensive effect was also assessed in rats with NO-deficient hypertension. In MVB precontracted with norepinephrine, BRW (alcohol-free lyophilized) induces a long-lasting endothelium-dependent vasodilation that is not reduced by indomethacin. Inhibition of NO-synthase by NG-nitro-L-arginine methyl ester (L-NAME) and guanylyl cyclase by 1H-[1,2,3] oxadiazolo [4,4-a]quinoxalin-1-one (ODQ) reduces the vasodilator effect of BRW. In vessels precontracted with norepinephrine and depolarized with KCl (25 Mm) or treated with Ca-dependent K channel blockers charybdotoxin (ChTx) plus apamin, the effect of BRW was significantly reduced. However, this effect is not affected by ATP-dependent K (KATP) channel blocker (glibenclamide). The residual vasodilator effect of BRW observed in vessels pretreated with ChTx plus apamin is completely abolished by ChTx plus apamin plus L-NAME. Concentrations of atropine, pyrilamine, yohimbine, and HOE 140 that significantly reduced the vasodilator effect of acetylcholine, histamine, clonidine, and bradykinin, respectively did not change the vasodilator effect of BRW. Chronic oral administration of BRW induced a significant reduction in systolic, mean and diastolic arterial pressure in rats with L-NAME hypertension. The present results demonstrated that vasodilator effect of BRW is dependent on endothelium-derived hyperpolarizing factor (EDHF) in combination with nitric oxide (NO). The antihypertensive effect of red wine demonstrated in the present study may play a significant role on the cardioprotective action of chronic red wine consumption.
红酒心脏保护作用所涉及的机制尚未完全阐明,但内皮依赖性血管舒张作用可能在该效应中发挥重要作用。进行了实验以确定一种巴西红酒(BRW)是否能诱导肠系膜血管床(MVB)舒张,并评估其对一氧化氮缺乏型高血压大鼠的降压作用。在去甲肾上腺素预收缩的MVB中,BRW(无酒精冻干物)可诱导持久的内皮依赖性血管舒张,吲哚美辛不能减弱这种舒张作用。NG-硝基-L-精氨酸甲酯(L-NAME)抑制一氧化氮合酶以及1H-[1,2,3]恶二唑并[4,4-a]喹喔啉-1-酮(ODQ)抑制鸟苷酸环化酶,均可降低BRW的血管舒张作用。在用去甲肾上腺素预收缩并经氯化钾(25 mM) depolarized或用钙依赖性钾通道阻滞剂蝎毒素(ChTx)加蜂毒明肽处理的血管中,BRW的作用显著降低。然而,这种作用不受ATP依赖性钾(KATP)通道阻滞剂(格列本脲)的影响。在经ChTx加蜂毒明肽预处理的血管中观察到的BRW残余血管舒张作用,可被ChTx加蜂毒明肽加L-NAME完全消除。分别能显著降低乙酰胆碱、组胺、可乐定和缓激肽血管舒张作用的阿托品、吡拉明、育亨宾和HOE 140的浓度,并未改变BRW的血管舒张作用。对L-NAME高血压大鼠长期口服BRW可导致收缩压、平均动脉压和舒张压显著降低。目前的结果表明,BRW的血管舒张作用依赖于内皮衍生的超极化因子(EDHF)与一氧化氮(NO)的联合作用。本研究中证明的红酒降压作用可能在长期饮用红酒的心脏保护作用中发挥重要作用。