Morishita R, Higaki J, Nakamura F, Tomita N, Yu H, Nagano M, Mikami H, Ogihara T
Department of Geriatric Medicine, Osaka University Medical School, Japan.
Blood Press Suppl. 1992;3:41-7.
This study was designed to investigate the effects of antihypertensive drugs on vascular hypertrophy and vascular angiotensin II in vivo in spontaneously hypertensive rats (SHR). Hydralazine (10 mg/kg/day), delapril (angiotensin converting enzyme inhibitor; 20 mg/kg/day), manidipine (calcium channel blocker; 10 mg/kg/day), and vehicle were given by gavage to four groups of SHR between 4 and 5 months of age. The aortic angiotensin II level was measured by highly sensitive radioimmunoassay coupled with high pressure liquid chromatography; aortic morphologic studies were performed. Each drug treatment effectively lowered blood pressure to the same level. However, the aortic wall thickness, medial-intimal areas, and wall to lumen ratio of abdominal aorta decreased significantly (p < 0.05, p < 0.01, p < 0.01, respectively) with delapril and manidipine but not hydralazine. Delapril significantly decreased aortic angiotensin II levels (p < 0.05), whereas manidipine treatment significantly increased them (p < 0.05). The aortic angiotensin II level was not changed by hydralazine. These results show that delapril and manidipine caused regression of hypertension-induced vascular hypertrophy in SHR. The probable mechanism of regression of aortic hypertrophy by delapril was inhibition of vascular angiotensin II formation, but the mechanism for manidipine was unclear.
本研究旨在探讨抗高血压药物对自发性高血压大鼠（SHR）体内血管肥厚及血管紧张素II的影响。给4至5月龄的四组SHR经口灌胃给予肼屈嗪（10毫克/千克/天）、地拉普利（血管紧张素转换酶抑制剂；20毫克/千克/天）、马尼地平（钙通道阻滞剂；10毫克/千克/天）及赋形剂。采用高灵敏度放射免疫分析结合高压液相色谱法测定主动脉血管紧张素II水平；进行主动脉形态学研究。每种药物治疗均有效将血压降至相同水平。然而，地拉普利和马尼地平可使腹主动脉的主动脉壁厚度、中膜-内膜面积及壁腔比显著降低（分别为p < 0.05、p < 0.01、p < 0.01），而肼屈嗪则无此作用。地拉普利显著降低主动脉血管紧张素II水平（p < 0.05），而马尼地平治疗则使其显著升高（p < 0.05）。肼屈嗪未改变主动脉血管紧张素II水平。这些结果表明，地拉普利和马尼地平可使SHR中高血压诱导的血管肥厚消退。地拉普利使主动脉肥厚消退的可能机制是抑制血管紧张素II的形成，而马尼地平的机制尚不清楚。
