Tan Mian-Shin, Chai Chee-Yin, Wu Jiunn-Ren, Yeh Jwu-Lai, Chen Ing-Jun, Kwan Aij-Lie, Jeng Arco Y, Yang Huey-Yu, Lee Meng-Hsun, Dai Zen-Kong
Faculty of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Taiwan.
Exp Biol Med (Maywood). 2006 Jun;231(6):948-53.
Pressure overload in the left ventricle of the heart follows a chronic and progressive course, resulting in eventual left heart failure and pulmonary hypertension (PH). The purpose of this research was to determine whether a differential pulmonary gene change of endothelin (ET)-1 and endothelial nitric oxide synthase (eNOS) occurred in adult rats with left ventricular overload. Eight groups of eight rats each were used (four rats with banding and four rats with sham operations). The rats underwent ascending aortic banding for 1 day, 2 weeks, 4 weeks, and 12 weeks before sacrifice. Significant medial hypertrophy of the pulmonary arterioles developed in two groups (4 and 12 weeks). Increased pulmonary arterial pressures were noted in three groups (1 day, 4 weeks, and 12 weeks). The aortic banding led to significant increases in pulmonary preproET-1 messenger RNA (mRNA) at 1 day and 12 weeks, and in pulmonary eNOS mRNA at 1 day and 12 weeks. In addition, there was increased pulmonary eNOS content at 1 day and 12 weeks in the banded rats, and increased lung cGMP levels were observed at 1 day. Increased lung ET-1 levels were also noted at 1 day (banded, 310 +/- 12 ng/g protein; sham, 201 +/- 12 ng/g protein; P < 0.01), 4 weeks (banded, 232 +/- 12 ng/g protein; sham, 201 +/- 12 ng/g protein; P < 0.01) and 12 weeks (banded, 242 +/- 12 ng/g protein; sham, 202 +/- 12 ng/g protein; P < 0.01). This indicates that the upregulated expression of ET-1 developed at least 4 weeks before eNOS expression in the course of PH, and, thus, medication against ET-1 could play a crucial role in treating PH with cardiac dysfunction secondary to aortic banding.
心脏左心室压力过载呈慢性进行性发展，最终导致左心衰竭和肺动脉高压（PH）。本研究的目的是确定成年左心室过载大鼠肺组织中内皮素（ET）-1和内皮型一氧化氮合酶（eNOS）基因变化是否存在差异。使用八组大鼠，每组八只（四只进行结扎手术，四只进行假手术）。在处死大鼠前，分别对其进行升主动脉结扎1天、2周、4周和12周。两组（4周和12周组）出现肺动脉小动脉明显的中膜肥厚。三组（1天、4周和12周组）出现肺动脉压力升高。主动脉结扎导致1天和12周时肺前体ET-1信使核糖核酸（mRNA）显著增加，1天和12周时肺eNOS mRNA也显著增加。此外，结扎大鼠在1天和12周时肺eNOS含量增加，1天时肺环磷酸鸟苷（cGMP）水平升高。1天（结扎组，310±12 ng/g蛋白；假手术组，201±12 ng/g蛋白；P<0.01）、4周（结扎组，232±12 ng/g蛋白；假手术组，201±12 ng/g蛋白；P<0.01）和12周（结扎组，242±12 ng/g蛋白；假手术组，202±12 ng/g蛋白；P<0.01）时肺ET-1水平也升高。这表明在PH病程中，ET-1表达上调至少比eNOS表达提前4周出现，因此，针对ET-1的药物在治疗主动脉结扎继发心脏功能障碍的PH中可能起关键作用。
