de Siqueira Rodrigo José Bezerra, Duarte Gloria Pinto, Magalhães Pedro Jorge Caldas, Lahlou Saad
Department of Physiology and Pharmacology, Federal University of Ceará, Fortaleza, CE, Brazil.
Nat Prod Commun. 2013 Aug;8(8):1167-70.
This study investigated the cardiovascular effects of the essential oil of Croton zehntneri (EOCZ) in deoxycorticosterone-acetate (DOCA)-salt hypertensive rats. Furthermore, in vitro experiments using isolated thoracic aortic rings were performed to assess the vascular effects of the EOCZ. In conscious hypertensive rats, intravenous (i.v.) injections of EOCZ (1-20 mg/kg) induced rapid (2-4 s) and dose-dependent hypotension and bradycardia (phase 1). The hypotension was followed by a significant pressor effect that was more evident at the higher doses (10 and 20 mg/kg) of EOCZ. Hypotension and bradycardia of EOCZ (phase 1) were abolished and respectively reversed into pressor and tachycardiac effects by methylatropine (1 mg/kg, i.v.) pretreatment. In isolated endothelium-intact aortic preparations, increasing concentrations (1-1000 microg/mL) of EOCZ relaxed the potassium-induced contraction in a concentration-dependent manner with an IC50 (geometric mean [95% confidence interval]) value of 202.0 [92.0-443.7] microg/mL. This vasorelaxant effect remained unaffected by either mechanical removal of functional vascular endothelium (IC50 = 189.0 [159.4-224.7] microg/mL) or the addition of atropine (1 microM) (IC50 = 158.6 [79.8-316.2] microg/mL) in the perfusion medium. These data show that i.v. administration of EOCZ in DOCA-salt hypertensive rats induces a vago-vagal reflex decreases in heart rate and blood pressure (phase 1). EOCZ may induce a second and delayed hypotension due to its direct endothelium-independent vasorelaxant effects, but it seems to be buffered by the pressor component (subsequent to phase 1) of EOCZ. This pattern of blood pressure and heart rate responses to EOCZ seems unaltered by DOCA-salt hypertension, as was similar to that previously reported in conscious normotensive rats.
本研究调查了泽氏巴豆精油(EOCZ)对醋酸脱氧皮质酮(DOCA)-盐高血压大鼠的心血管作用。此外,还进行了使用离体胸主动脉环的体外实验,以评估EOCZ的血管效应。在清醒的高血压大鼠中,静脉注射EOCZ(1-20mg/kg)可诱导快速(2-4秒)且剂量依赖性的低血压和心动过缓(第1阶段)。低血压之后是明显的升压效应,在较高剂量(10和20mg/kg)的EOCZ时更明显。EOCZ引起的低血压和心动过缓(第1阶段)可被甲基阿托品(1mg/kg,静脉注射)预处理消除,并分别逆转升压和心动过速效应。在离体的完整内皮主动脉制剂中,EOCZ浓度增加(1-1000μg/mL)以浓度依赖性方式松弛钾诱导的收缩,IC50(几何平均值[95%置信区间])值为202.0[92.0-443.7]μg/mL。这种血管舒张作用不受功能性血管内皮的机械去除(IC50 = 189.0[159.4-224.7]μg/mL)或灌注介质中添加阿托品(1μM)(IC50 = 158.6[79.8-316.2]μg/mL)的影响。这些数据表明,在DOCA-盐高血压大鼠中静脉注射EOCZ可诱导迷走-迷走反射,使心率和血压降低(第1阶段)。EOCZ可能因其直接的非内皮依赖性血管舒张作用而诱导第二次延迟性低血压,但似乎被EOCZ的升压成分(第1阶段之后)所缓冲。EOCZ引起的这种血压和心率反应模式似乎不受DOCA-盐高血压的影响,与之前在清醒的正常血压大鼠中报道的相似。