Sharifi A M, Li J S, Endemann D, Schiffrin E L
MRC Multidisciplinary Research Group on Hypertension, Clinical Research Institute of Montréal, University of Montréal, Québec, Canada.
J Hypertens. 1998 Apr;16(4):457-66. doi: 10.1097/00004872-199816040-00007.
To determine whether an angiotensin converting enzyme inhibitor, enalapril, and a dihydropyridine calcium channel antagonist, amlodipine, regress the altered structure, media composition, and vascular relaxation of small arteries of spontaneously hypertensive rats.
Spontaneously hypertensive rats aged 10 weeks were treated for 12 weeks with 10 mg/kg per day enalapril or 10-20 mg/kg per day amlodipine and compared with age-matched untreated spontaneously hypertensive rats. Small coronary, renal, mesenteric, and femoral arteries (lumen diameter 200-250 microm) were studied isometrically on a wire myograph, and mesenteric arteries isobarically as pressurized vessels. The composition of the vascular media of the latter was studied by electron microscopy.
Blood pressure, and cardiac and aortic hypertrophy were reduced in treated spontaneously hypertensive rats. Treatment significantly decreased media thickness and media: lumen ratio of coronary, renal, mesenteric, and femoral small arteries studied isometrically and of pressurized mesenteric small arteries. Media cross-sectional area was smaller for coronary arteries studied isometrically and mesenteric arteries studied isobarically. Electron microscopic analysis revealed an increase in collagen: elastin ratio in the media of spontaneously hypertensive rat vessels, and a decrease under treatment to levels found in Wistar-Kyoto rats, with no significant changes detected in smooth muscle cells. The amplitude of contractions induced by acetylcholine on wire-myograph-mounted mesenteric arteries from spontaneously hypertensive rats were decreased by treatment, and relaxation of pressurized arteries induced by acetylcholine was normalized.
Treatment of spontaneously hypertensive rats with enalapril or with amlodipine resulted in regression of cardiovascular hypertrophy and amelioration of endothelial dysfunction. Morphometric results obtained using an isometric myograph and a pressurized preparation to study rat small arteries were closely correlated. Regression of structural remodeling in small arteries was outward hypotrophic, with a reduction in the collagen: elastin ratio, and without net change in the absolute and relative volumes of smooth muscle and number of smooth muscle layers.
确定血管紧张素转换酶抑制剂依那普利和二氢吡啶类钙通道拮抗剂氨氯地平是否能使自发性高血压大鼠小动脉结构改变、中膜成分及血管舒张功能恢复正常。
10周龄的自发性高血压大鼠每日给予10mg/kg依那普利或10 - 20mg/kg氨氯地平治疗12周，并与年龄匹配的未治疗自发性高血压大鼠进行比较。使用线肌张力测定仪对等长收缩的小冠状动脉、肾动脉、肠系膜动脉和股动脉（管腔直径200 - 250微米）进行研究，对肠系膜动脉作为压力血管进行等压研究。通过电子显微镜研究后者血管中膜的成分。
治疗后的自发性高血压大鼠血压、心脏和主动脉肥大减轻。治疗显著降低了等长收缩研究的冠状动脉、肾动脉、肠系膜动脉和股动脉以及等压研究的肠系膜小动脉的中膜厚度和中膜与管腔比值。等长收缩研究的冠状动脉和等压研究的肠系膜动脉的中膜横截面积较小。电子显微镜分析显示，自发性高血压大鼠血管中膜的胶原蛋白与弹性蛋白比值增加，治疗后降低至Wistar - Kyoto大鼠的水平，平滑肌细胞未检测到显著变化。治疗使自发性高血压大鼠线肌张力测定仪上肠系膜动脉由乙酰胆碱诱导的收缩幅度降低，乙酰胆碱诱导的压力动脉舒张恢复正常。
依那普利或氨氯地平治疗自发性高血压大鼠可导致心血管肥大消退和内皮功能障碍改善。使用等长肌张力测定仪和压力制备法研究大鼠小动脉获得的形态学结果密切相关。小动脉结构重塑的消退是向外萎缩性的，胶原蛋白与弹性蛋白比值降低，平滑肌的绝对和相对体积以及平滑肌层数无净变化。
