Magalhães Pedro Jorge Caldas, Lahlou Saad, Jucá Davi Matthews, Coelho-de-Souza Lívia Noronha, da Frota Pedro Thiago Tibúrcio, da Costa Adriana Maria Gurgel, Leal-Cardoso José Henrique
Departamento de Fisiologia e Farmacologia, Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, CE, Brazil.
Fundam Clin Pharmacol. 2008 Apr;22(2):169-77. doi: 10.1111/j.1472-8206.2008.00571.x.
Previously, we reported that essential oil of Croton nepetaefolius (EOCN) decreases blood pressure in normotensive rats, an effect that seems resulting from its vasodilatory action directly upon vascular smooth muscle. In the present study, we aimed to study the role of endothelium-nitric oxide pathway in the mediation of vasodilatory effects of EOCN and two of its constituents, methyleugenol and alpha-terpineol, using rat isolated thoracic aorta and mesenteric vascular bed preparations. EOCN (1-300 microg/mL), in a concentration-dependent manner, relaxed isolated endothelium-intact aortic rings precontracted with KCl 60 mM, with an IC(50) value of 26.7 (14.7-48.2) microg/mL. Either pretreatment of the tissue with L-NAME, a nitric oxide synthase inhibitor, or mechanical endothelium removal increased significantly the IC(50) value to 66.6 (52.7-84.1) or 105.6 (91.3-122.2) microg/mL, respectively. In endothelium-intact aortic rings precontracted with norepinephrine, EOCN (10-200 microg/mL) produced a vasorelaxant action which was decreased by the pretreatment of the aortic rings with methylene blue, a guanylate cyclase inhibitor. In mesenteric bed preparations perfused under constant pressure, EOCN reverted the reduction of mesenteric flow caused by KCl (60 mM), an effect that was attenuated by L-NAME. Vasodilator responses to EOCN in mesenteric bed preparations were mimicked by methyleugenol and alpha-terpineol, and were also significantly reduced in the presence of L-NAME. In conclusion, EOCN has vasorelaxant effects in both a resistance vascular bed and in a conduit artery. They seem attributed, at least in part, to the actions of its main constituents methyleugenol and alpha-terpineol and appear partially dependent upon the integrity of a functional vascular endothelium. Inhibition of other transduction pathways may be involved in the mediation of these effects.
此前,我们报道了巴豆叶精油(EOCN)可降低正常血压大鼠的血压,该作用似乎源于其对血管平滑肌的直接舒张作用。在本研究中,我们旨在利用大鼠离体胸主动脉和肠系膜血管床标本,研究内皮-一氧化氮途径在介导EOCN及其两种成分甲基丁香酚和α-松油醇舒张血管作用中的作用。EOCN(1 - 300μg/mL)以浓度依赖性方式使预先用60 mM KCl收缩的离体完整内皮主动脉环舒张,IC50值为26.7(14.7 - 48.2)μg/mL。用一氧化氮合酶抑制剂L - NAME预处理组织或机械去除内皮,均可使IC50值分别显著增加至66.6(52.7 - 84.1)或105.6(91.3 - 122.2)μg/mL。在预先用去甲肾上腺素收缩的完整内皮主动脉环中,EOCN(10 - 200μg/mL)产生舒张血管作用,而用鸟苷酸环化酶抑制剂亚甲蓝预处理主动脉环可减弱该作用。在恒压灌注的肠系膜床标本中,EOCN可逆转由KCl(60 mM)引起的肠系膜血流减少,该作用被L - NAME减弱。甲基丁香酚和α-松油醇可模拟肠系膜床标本对EOCN的舒张血管反应,且在L - NAME存在时也显著降低。总之,EOCN在阻力血管床和输送动脉中均具有舒张血管作用。这些作用似乎至少部分归因于其主要成分甲基丁香酚和α-松油醇的作用,且似乎部分依赖于功能性血管内皮的完整性。其他转导途径的抑制可能参与了这些作用的介导。