Devlin A M, Davidson A O, Gordon J F, Campbell A M, Morton J J, Reid J L, Dominiczak A F
Department of Medicine and Therapeutics, Gardiner Institute, Western Infirmary, Glasgow, UK.
J Hum Hypertens. 1995 Jun;9(6):497-500.
Flow cytometry DNA analysis has been used to measure the percentage of aortic vascular smooth muscle cells in G2 + M phase of the cell cycle in mature stroke-prone spontaneously hypertensive rats (SHRSP). The effects of three different pharmacological interventions on the cell cycle parameters have also been studied. Vascular smooth muscle cells isolated from SHRSP have significantly elevated G2 + M phase of the cell cycle compared with cells from the normotensive reference strain, Wistar-Kyoto (WKY). This observation reflects an increased tetraploid and octaploid cell populations in vivo. Treatment with a combination of hydralazine and hydrochlorothiazide had no effect on the percentage of cells in G2 + M phase of the cell cycle. Treatments with angiotensin converting enzyme inhibitor, perindopril or AT1 receptor antagonist, losartan, resulted in an equivalent blood pressure-lowering effect to that obtained with hydralazine/hydrochlorothiazide. In contrast to hydralazine/hydrochlorothiazide, these two treatments resulted in a highly significant regression of vascular smooth muscle polyploidy in the SHRSP. We hypothesise that angiotensin II plays an important role in cell cycle regulation in that, alone or in conjunction with one of the inhibitory proteins, it is able to stop the cell cycle progression after endoduplication but before the cytoplasmic division. Pharmacological interventions which remove an excess of angiotensin II may allow the cells to re-enter the cell cycle thus resulting in the regression of vascular smooth muscle polyploidy and improved arterial compliance.
流式细胞术DNA分析已被用于测量成熟的易中风自发性高血压大鼠（SHRSP）细胞周期中G2 + M期主动脉血管平滑肌细胞的百分比。还研究了三种不同药物干预对细胞周期参数的影响。与正常血压对照品系Wistar-Kyoto（WKY）的细胞相比，从SHRSP分离的血管平滑肌细胞的细胞周期G2 + M期显著升高。这一观察结果反映了体内四倍体和八倍体细胞群体的增加。肼屈嗪和氢氯噻嗪联合治疗对细胞周期G2 + M期的细胞百分比没有影响。用血管紧张素转换酶抑制剂培哚普利或AT1受体拮抗剂氯沙坦治疗，产生的降压效果与肼屈嗪/氢氯噻嗪相当。与肼屈嗪/氢氯噻嗪相反，这两种治疗导致SHRSP中血管平滑肌多倍体显著消退。我们假设血管紧张素II在细胞周期调节中起重要作用，即单独或与一种抑制蛋白一起，它能够在内复制后但在细胞质分裂前阻止细胞周期进程。去除过量血管紧张素II的药物干预可能使细胞重新进入细胞周期，从而导致血管平滑肌多倍体消退并改善动脉顺应性。
