Ollerenshaw J D, Heagerty A M, West K P, Swales J D
Department of Medicine, Leicester Royal Infirmary, UK.
J Hypertens. 1988 Sep;6(9):733-8. doi: 10.1097/00004872-198809000-00007.
In order to examine the effects of imposing an acute pressure load upon vascular structure and phosphoinositide hydrolysis, aortic medial thickness, cross-sectional area, cell nuclear counts and inositol phosphate accumulation were measured in Wistar rats with experimental coarctation and sham-operated controls at 3, 9 and 20 days after surgery. Compared to sham-operated animals, rats with coarctation had significantly higher carotid artery pressures throughout the study. Below the ligature, femoral arterial pressure was significantly lower in animals with coarctation. Proximal to the coarctation, there was an increase in aortic medial cross-sectional area and medial thickness but no increase in nuclear counts, suggesting the induction of hypertrophy; statistically significant changes were present at 9 and 20 days. Distal to the ligature only small structural changes were observed indicating some atrophy had occurred. Inositol phosphate accumulation had increased slightly at 3 days in proximal aortae from ligatured rats, and was significantly raised at 9 and 20 days; no such changes were recorded below the coarctation. These data indicate that the increased load upon the proximal aorta initiates increased inositol phosphate production through local mechanisms. Whilst a causal link has not been conclusively established between phosphoinositide turnover and hypertrophy, the association between the two in these studies is consistent with the hypothesis that the induction of increased cell phosphoinositide metabolism contributes, at least in part, to the proximal aortic structural changes observed in this model.
为研究急性压力负荷对血管结构和磷酸肌醇水解的影响,在术后3天、9天和20天,对实验性缩窄的Wistar大鼠及假手术对照组大鼠测量了主动脉中膜厚度、横截面积、细胞核计数以及肌醇磷酸蓄积情况。与假手术动物相比,在整个研究过程中,缩窄大鼠的颈动脉压力显著更高。在结扎部位下方,缩窄动物的股动脉压力显著更低。在缩窄近端,主动脉中膜横截面积和中膜厚度增加,但细胞核计数未增加,提示发生了肥大;在9天和20天出现了具有统计学意义的变化。在结扎部位远端,仅观察到微小的结构变化,表明发生了一些萎缩。在结扎大鼠近端主动脉中,肌醇磷酸蓄积在3天时略有增加,在9天和20天时显著升高;在缩窄下方未记录到此类变化。这些数据表明,近端主动脉上增加的负荷通过局部机制引发了肌醇磷酸生成增加。虽然尚未在磷酸肌醇周转与肥大之间最终确立因果联系,但在这些研究中二者之间的关联与以下假说一致,即细胞磷酸肌醇代谢增加的诱导至少部分促成了该模型中观察到的近端主动脉结构变化。