Juric Danijel, Wojciechowski Peter, Das Dipak K, Netticadan Thomas
Cardiovascular Research Center, University of Connecticut School of Medicine, Farmington, CT 06030-1110, USA.
Am J Physiol Heart Circ Physiol. 2007 May;292(5):H2138-43. doi: 10.1152/ajpheart.00852.2006.
This study was designed to examine the effects of the antioxidant resveratrol on cardiac structure and function in pressure overload (PO)-induced cardiac hypertrophy. Male Sprague-Dawley rats were subjected to sham operation and the aortic banding procedure. A subgroup of sham control and aortic-banded rats were treated with resveratrol for 2 wk after surgery. Echocardiographic analysis of cardiac structure and function along with Western blot analysis of endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), and redox factor-1 (ref-1) were performed in all groups after 4 wk of surgery. Banded rats showed significantly increased left ventricle-to-body weight ratio. Echocardiographic analysis showed that the interventricular septal wall thickness and left ventricular posterior wall thickness at systole and diastole were significantly increased in banded rats. Also, a significant increase in isovolumic relaxation time was observed in banded rats. Measured eNOS, iNOS, and ref-1 protein levels were significantly reduced in banded rats. Resveratrol treatment prevented the above changes in cardiac structure, function, and protein expression in banded rats. Aortic banding after 4 wk resulted in concentric remodeling and impaired contractile function due to PO on the heart. The 2-wk treatment with resveratrol was found to abolish PO-induced cardiac hypertrophy. Resveratrol may therefore be beneficial against PO-induced cardiac hypertrophy found in clinical settings of hypertension and aortic valve stenosis.
本研究旨在探讨抗氧化剂白藜芦醇对压力超负荷(PO)诱导的心脏肥大模型中心脏结构和功能的影响。将雄性Sprague-Dawley大鼠进行假手术和主动脉缩窄手术。假手术对照组和主动脉缩窄组的一个亚组在术后用白藜芦醇治疗2周。术后4周,对所有组进行心脏结构和功能的超声心动图分析以及内皮型一氧化氮合酶(eNOS)、诱导型一氧化氮合酶(iNOS)和氧化还原因子-1(ref-1)的蛋白质印迹分析。主动脉缩窄大鼠的左心室与体重比显著增加。超声心动图分析显示,主动脉缩窄大鼠在收缩期和舒张期的室间隔厚度和左心室后壁厚度显著增加。此外,主动脉缩窄大鼠的等容舒张时间显著延长。主动脉缩窄大鼠中检测到的eNOS、iNOS和ref-1蛋白水平显著降低。白藜芦醇治疗可防止主动脉缩窄大鼠出现上述心脏结构、功能和蛋白质表达的变化。4周后的主动脉缩窄导致心脏因压力超负荷而出现向心性重塑和收缩功能受损。发现白藜芦醇2周的治疗可消除压力超负荷诱导的心脏肥大。因此,白藜芦醇可能对高血压和主动脉瓣狭窄临床环境中出现的压力超负荷诱导的心脏肥大有益。