细胞内游离钙在ACEI逆转SHR血管重构中的作用

Effect of Intracellular Calcium in Reversing Vascular Remodeling in Hypertension by ACEI Therapy

目的 :探讨细胞内游离钙在血管紧张素转换酶抑制剂 (ACEI)逆转自发性高血压大鼠 (SHR)血管重构中的作用。方法 :采用SHR、正常血压大鼠 (WKY)配对 ,服药前后对比及离体血管、淋巴细胞药物处理研究。结果 :①SHR与WKY比较有以下血管重构现象 :血管内膜有WBC粘附和侵袭 ,中层血管平滑肌细胞 (VSMC)排列紊乱、纤维成分增多 ;血管内皮细胞及VSMC线粒体增多 ,体密度增加、肿胀 ,肌浆网扩张 ,比表面减少。②SHR外周淋巴细胞 [Ca2 + ]i,主动脉平滑肌45Ca静息内流 ,血浆血管紧张素Ⅱ浓度 [ATⅡ ]均较WKY显著增加 ;③ACEI治疗后SHR血管重构现象得到逆转 ,血浆 [ATⅡ ]、淋巴细胞 [Ca2 + ]i、主动脉平滑肌45Ca静息内流均降低 ;④离体情况下ATⅡ能使SHR、WKY主动脉平滑肌45Ca静息内流及淋巴细胞 [Ca2 + ]i增加 ,ACEI使以上指标下降。结论 :ACEI能有效逆转高血压血管重构现象 。

Objective: to determine the effect of intracellular calcium in reversing vascular remodeling in SHR by ACEI therapy. Methods: The changes of mesenteric artery in SHR and WKY before and after ACEI treatment,and the directly effect of calcium metabolism by ATⅡ and ACEI stimulation were observed. Results: 1) Compared with WKY,the vascular remodeling in SHR was featured by: vessel adherence and subendothelial invasion with WBC,increased fibrocytes and irregularly arranged smooth muscle cells in middle layer,and increased number of mitochondria,with swelling and degeneration,within smooth muscle cells. The sarcoplasmic reticulum became swollen as well. 2) The intralymphocytic free calcium concentration ([Ca 2+ ]i) and 45 Ca influx of aorta smooth muscle and [ATⅡ] were significantly higher in SHR; 3) After ACEI treatment,the blood pressure,[Ca 2+ ]i, 45 Ca influx of aorta smooth muscle and [ATⅡ] were decreased,the change of mitochondria and the vascular remodeling were reversed. The case fatality rate was declined. 4) ATⅡ can directly increased intralymphocytic [Ca 2+ ]i and 45 Ca influx of aorta smooth muscle,but ACEI can directly decreased [Ca 2+ ]i and 45 Ca influx of aorta smooth muscle in SHR and WKY. Conclusions: ACEI therapy could reversed the vascular remodeling in SHR. The intracellular calcium changes may be involved to the mechanism of reversing vascular remodeling by ACEI treatment.