Eto Masato, Toba Kenji, Akishita Masahiro, Kozaki Koichi, Watanabe Tokumitsu, Kim Seungbum, Hashimoto Masayoshi, Sudoh Noriko, Yoshizumi Masao, Ouchi Yasuyoshi
Department of Geriatric Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
Hypertens Res. 2003 Dec;26(12):991-8. doi: 10.1291/hypres.26.991.
Increased short-term blood pressure variability is known to be associated with hypertensive target organ damage. Sinoaortic denervation (SAD) induces a marked increase in blood pressure lability without affecting the average blood pressure level. The aim of this study was to investigate the effects of blood pressure lability on endothelial vasomotor function and neointimal formation after balloon injury in SAD rats. Direct longterm measurement of mean arterial pressure showed no significant difference in the average of mean arterial pressure between the SAD group and sham-operated control group. In contrast, the standard deviation of mean arterial pressure, as an index of blood pressure lability, was 3-fold greater in SAD rats. To study endothelial function, isometric tension of aortic rings was measured 4 weeks after SAD or sham operation. Endothelium-dependent vasorelaxation induced by acetylcholine was significantly reduced in the SAD group (20% reduction at maximum relaxation). Endothelium-independent vasorelaxation induced by sodium nitroprusside was similar in each group. Acetylcholine-induced NO release from aortic rings was significantly reduced in the SAD group. Next, we examined neointimal formation in carotid arteries in SAD and sham-operated rats at 2 weeks after balloon injury. The neointimal-to-medial area ratio in the SAD group was 50% higher than that in the sham-operated group. The percentage of proliferating cell nuclear antigen-positive cells in the intima was significantly higher in the SAD group. These findings suggest that increased blood pressure lability, independently of average blood pressure level, impairs endothelial function by inhibiting NO production, enhances neointimal formation after balloon injury, and may thereby contribute to atherogenesis.
已知短期血压变异性增加与高血压靶器官损害有关。去窦弓神经支配(SAD)可导致血压不稳定性显著增加,而不影响平均血压水平。本研究的目的是探讨血压不稳定性对SAD大鼠球囊损伤后内皮血管运动功能和新生内膜形成的影响。直接长期测量平均动脉压显示,SAD组和假手术对照组之间的平均动脉压平均值无显著差异。相比之下,作为血压不稳定性指标的平均动脉压标准差在SAD大鼠中高出3倍。为了研究内皮功能,在SAD或假手术后4周测量主动脉环的等长张力。SAD组中乙酰胆碱诱导的内皮依赖性血管舒张显著降低(最大舒张时降低20%)。硝普钠诱导的非内皮依赖性血管舒张在每组中相似。SAD组中乙酰胆碱诱导的主动脉环NO释放显著减少。接下来,我们在球囊损伤后2周检查了SAD和假手术大鼠颈动脉中的新生内膜形成。SAD组的新生内膜与中膜面积比比假手术组高50%。SAD组内膜中增殖细胞核抗原阳性细胞的百分比显著更高。这些发现表明,血压不稳定性增加,独立于平均血压水平,通过抑制NO生成损害内皮功能,增强球囊损伤后的新生内膜形成,并可能因此促进动脉粥样硬化的发生。