The effects of perindopril on vascular smooth muscle polyploidy in stroke‐prone spontaneously hypertensive rats
The effects of perindopril on vascular smooth muscle polyploidy in stroke‐prone spontaneously hypertensive rats
复制标题
培哚普利对脑卒中易发性高血压大鼠血管平滑肌多倍体的影响
DOI：
10.1097/00004872-199502000-00008
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发表时间：
1995
影响因子：
4.9
通讯作者：
A. Dominiczak
中科院分区：
文献类型：
--
作者：
A. M. Devlin;John F. Gordon;A. O. Davidson;J. Clark;C. Hamilton;J. Morton;Ailsa M. Campbell;J. Reid;A. Dominiczak
目的研究易卒中型自发性高血压大鼠（SHRSP）和正常血压Wistar-Kyoto（WKY）大鼠主动脉平滑肌细胞的增殖动力学和血管平滑肌细胞的倍体，并观察血管紧张素转换酶（ACE）抑制剂培哚普利对这些参数的影响。实验设计：实验组为年轻（年龄<20周龄）和老年（年龄> 20周龄）未治疗的WKY大鼠和未治疗的SHRSP; SHRSP用培哚普利治疗，年龄和性别匹配的对照组SHRSP; SHRSP用肼苯哒嗪和氢氯噻嗪治疗，年龄和性别匹配的对照组SHRSP。测定培哚普利治疗SHRSP 30天对血管平滑肌多倍体和生长动力学的影响，并与等效降压剂量的肼屈嗪和氢氯噻嗪的影响进行比较。方法采用流式细胞术检测血管平滑肌细胞的DNA倍体。在培养的主动脉细胞上进行生长曲线。采用抗体捕获法测定血浆肾素活性，放射免疫法测定血浆血管紧张素II（Ang II），比色法测定血浆ACE活性。通过测量心脏重量：体重和左心室+间隔重量：体重比来评价心脏肥大。结果SHRSP可显著延长细胞周期G2 + M期。培哚普利治疗导致SHRSP的多倍体显著减少，而肼苯哒嗪和氢氯噻嗪治疗对细胞周期G2 + M期细胞的百分比没有影响。培哚普利治疗后多倍体的消退与Ang II浓度和ACE活性的显著降低以及心脏肥大的显著消退相关。培哚普利治疗并不改变培养的SHRSP血管平滑肌细胞有丝分裂的增加。结论血管紧张素转换酶抑制剂可降低大导管动脉平滑肌细胞的多倍性。这种类型的血管保护是由降低的Ang II介导的，并且可能是由增加的激肽水平介导的，而不是由单独的扩张作用介导的。
Objective To quantify vascular smooth muscle polyploidy and growth kinetics in aortic cells from stroke-prone spontaneously hypertensive rats (SHRSP) and from normotensive Wistar-Kyoto (WKY) rats, and to examine the effects of treatment with the angiotensin converting enzyme (ACE) inhibitor perindopril on these parameters. Design The following experimental groups were used: young (age <20 weeks) and old (age > 20 weeks) untreated WKY rats and untreated SHRSP; SHRSP treated with perindopril, and age- and sex-matched control SHRSP; and SHRSP treated with hydralazine and hydrochlorothiazide and age- and sex-matched control SHRSP. The effects of treatment of the SHRSP with perindopril for 30 days on vascular smooth muscle polyploidy and growth kinetics were measured and compared with the effects of equivalent antihypertensive doses of hydralazine and hydrochlorothiazide. Methods Vascular smooth muscle polyploidy was measured using flow-cytometry DNA analysis of freshly harvested cells. Growth curves were performed on cultured aortic cells. Plasma renin activity was measured by an antibody-trapping method, plasma angiotensin II (Ang II) by radioimmunoassay and plasma ACE activity by a colorimetric method. Cardiac hypertrophy was evaluated by measuring the heart weight: body weight and left ventricle + septum weight: body weight ratios. Results The SHRSP had markedly and significantly elevated G2 + M phase of the cell cycle. Treatment with perindopril resulted in a significant reduction in polyploidy in the SHRSP, whereas treatment with hydralazine and hydrochlorothiazide had no effect on the percentage of cells in the G2 + M phase of the cell cycle. The regression of polyploidy after treatment with perindopril was associated with a significant reduction in the concentration of Ang II and ACE activity, and with a significant regression of cardiac hypertrophy. Increased mitogenesis of cultured vascular smooth muscle cells from the SHRSP was not altered by treatment with perindopril. Conclusions ACE inhibition reduces vascular smooth muscle polyploidy in large conduit arteries. This type of vascular protection is mediated by the reduced Ang II and possibly by increased kinins level, rather than by the hypotensive effect alone.