Franova Sona, Nosalova Gabriela, Pechanova Olga, Sutovska Martina
Department of Pharmacology, Jessenius Faculty of Medicine, Comenius University, Martin, Slovakia.
J Pharm Pharmacol. 2007 May;59(5):727-32. doi: 10.1211/jpp.59.5.0014.
The aims of the study were to investigate the short and long-term effects of Provinol (red wine polyphenolic compounds) on tracheal smooth muscle reactivity using an in-vitro model of ovalbumin-induced airway inflammation in guinea-pig trachea, and to evaluate the role of nitric oxide (NO) in the bronchodilatory effect of Provinol. The amplitude of tracheal smooth muscle contraction in response to mediators of bronchoconstriction - histamine (10 nM-1 mM), acetylcholine (10 nM-1 mM) and to allergen (ovalbumin 10(-5)-10(-3) g mL(-1)) was used as a parameter of tracheal smooth muscle reactivity. To test the short-term effects of Provinol, isolated tracheal strips were pre-treated for 30 min with Provinol (10(-4) mg mL(-1)) alone or in combination with Nomega-nitro-L-arginine methyl ester (L-NAME; 10(-6) mol L(-1)). To test the long-term effects of Provinol, isolated tracheal strips were prepared from guinea pigs that had been treated for 14 days with Provinol (20 mg kg(-1) per day) alone or in combination with L-NAME (40 mg kg(-1) per day). Incubation of tracheal smooth muscle with Provinol decreased the amplitude of contraction in response to ovalbumin, histamine and acetylcholine. The non-selective NO synthase inhibitor L-NAME partially abolished the effect of Provinol on acetylcholine and ovalbumin-induced but not histamine-induced bronchoconstriction. A similar profile was observed after 14 days' oral administration of Provinol. In conclusion, Provinol inhibited the allergen- and spasmogen-induced contraction of tracheal smooth muscle in ovalbumin-sensitized guinea pigs via a mechanism that was mediated at least partially through the metabolism of NO.
本研究的目的是使用卵清蛋白诱导的豚鼠气管气道炎症体外模型,研究普罗维诺(红酒多酚化合物)对气管平滑肌反应性的短期和长期影响,并评估一氧化氮(NO)在普罗维诺支气管舒张作用中的作用。将气管平滑肌对支气管收缩介质——组胺(10 nM - 1 mM)、乙酰胆碱(10 nM - 1 mM)和变应原(卵清蛋白10(-5)-10(-3) g mL(-1))的收缩幅度用作气管平滑肌反应性的参数。为了测试普罗维诺的短期作用,将离体气管条单独用普罗维诺(10(-4) mg mL(-1))或与Nω-硝基-L-精氨酸甲酯(L-NAME;10(-6) mol L(-1))联合预处理30分钟。为了测试普罗维诺的长期作用,从单独用普罗维诺(每天20 mg kg(-1))或与L-NAME(每天40 mg kg(-1))联合处理14天的豚鼠制备离体气管条。用普罗维诺孵育气管平滑肌可降低对卵清蛋白、组胺和乙酰胆碱的收缩幅度。非选择性NO合酶抑制剂L-NAME部分消除了普罗维诺对乙酰胆碱和卵清蛋白诱导的支气管收缩的作用,但对组胺诱导的支气管收缩无此作用。口服普罗维诺14天后观察到类似的情况。总之,普罗维诺通过至少部分由NO代谢介导的机制,抑制卵清蛋白致敏豚鼠中变应原和致痉剂诱导的气管平滑肌收缩。