Ferrante F, Abbate F, Ciriaco E, Laurà R, Amenta F
Dipartimento di Scienze Cardiovascolari e Respiratorie, Università La Sapienza, Rome, Italy.
J Hypertens. 1994 May;12(5):523-31.
To investigate the influence of hypertension and of treatment with the vasodilator hydralazine or with the dihydropyridine calcium antagonist isradipine on the morphology of the thoracic aorta in spontaneously hypertensive rats (SHR).
The systolic blood pressure (SBP), body weight and morphology of the thoracic aorta were evaluated. The ultrastructure of the smooth muscle component of the aorta and of the tunica intima were analysed by transmission and scanning electron microscopy.
The SHR were divided into three groups: a control group, which was left untreated, and two treatment groups, one with 1 mg/kg per day hydralazine and the other with 0.1 mg/kg per day isradipine. Three age-matched groups of Wistar-Kyoto (WKY) rats were included in the study: one group was left untreated and was used as a normotensive reference group, the other two groups were treated with 1 mg/kg per day hydralazine or with 0.1 mg/kg per day isradipine.
The SBP did not change in the WKY rats treated with hydralazine, with isradipine or untreated, but was significantly increased in the SHR as a function of age. Both hydralazine and isradipine significantly reduced the SBP in the SHR after the second week of treatment. Light microscopy analysis of the thoracic aorta revealed thickening of the wall of the tunica media as well as an increase in the wall: lumen ratio in the SHR. Treatment with hydralazine had no effect on the morphometric parameters evaluated, whereas isradipine administration significantly reduced the thickening of both the wall and the tunica media of the aorta, and reduced the wall: lumen ratio. No significant modifications in the structure of the thoracic aorta were noticed in the hydralazine- or isradipine-treated WKY rats compared with untreated WKY rats. Transmission and scanning electron microscopy analysis demonstrated in control SHR hypertrophy of smooth muscle cells of the tunica media, an increased size and impairment of the internal elastic lamina, and a widening of the subendothelial space. Hypertrophy of the endothelium was also noticeable in the SHR. Treatment with isradipine reduced the hypertrophy of smooth muscle cells of the tunica media and the structural impairment of the tunica intima. No effect of isradipine treatment on the morphology of the aorta was noticed in the WKY rats.
The present results show that the effect of isradipine was different from that of hydralazine. Both compounds lowered the SBP, but only isradipine countered the structural changes of the aorta in the SHR. The effect of isradipine administration is particularly pronounced on the hypertension-dependent changes of endothelium. This suggests that isradipine may have a protective effect on the endothelium.
研究高血压以及使用血管扩张剂肼屈嗪或二氢吡啶类钙拮抗剂伊拉地平治疗对自发性高血压大鼠（SHR）胸主动脉形态的影响。
评估收缩压（SBP）、体重和胸主动脉形态。通过透射电子显微镜和扫描电子显微镜分析主动脉平滑肌成分和内膜的超微结构。
将SHR分为三组：一组为未治疗的对照组，另外两组为治疗组，一组每天给予1mg/kg肼屈嗪，另一组每天给予0.1mg/kg伊拉地平。研究纳入了三组年龄匹配的Wistar-Kyoto（WKY）大鼠：一组未治疗作为正常血压参考组，另外两组分别每天给予1mg/kg肼屈嗪或0.1mg/kg伊拉地平。
接受肼屈嗪、伊拉地平治疗或未治疗的WKY大鼠的SBP没有变化，但SHR的SBP随年龄显著升高。治疗第二周后，肼屈嗪和伊拉地平均显著降低了SHR的SBP。胸主动脉的光学显微镜分析显示，SHR的中膜壁增厚以及壁与腔比值增加。肼屈嗪治疗对所评估的形态学参数没有影响，而给予伊拉地平显著减少了主动脉壁和中膜的增厚，并降低了壁与腔比值。与未治疗的WKY大鼠相比，接受肼屈嗪或伊拉地平治疗的WKY大鼠胸主动脉结构没有明显改变。透射电子显微镜和扫描电子显微镜分析显示，对照SHR的中膜平滑肌细胞肥大，内弹性膜尺寸增加且受损，内皮下间隙增宽。SHR的内皮也有肥大现象。给予伊拉地平减少了中膜平滑肌细胞肥大和内膜的结构损伤。在WKY大鼠中未观察到伊拉地平治疗对主动脉形态的影响。
目前的结果表明，伊拉地平的作用与肼屈嗪不同。两种化合物均降低了SBP，但只有伊拉地平抵消了SHR主动脉的结构变化。给予伊拉地平的作用在内皮的高血压依赖性变化方面尤为明显。这表明伊拉地平可能对内皮有保护作用。
