Ishimitsu T, Uehara Y, Ishii M, Ikeda T, Matsuoka H, Sugimoto T
2nd Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
Hypertension. 1988 Jul;12(1):46-51. doi: 10.1161/01.hyp.12.1.46.
The vascular wall has the capacity to produce thromboxane A2. However, the role of vascular thromboxane A2 is still uncertain. In this study, we examined the relationship between vascular thromboxane A2 generation and vascular smooth muscle cell growth in spontaneously hypertensive rats (SHR). Vascular thromboxane A2 generation was significantly enhanced by 49% in 5-week-old and by 117% in 15-week-old SHR as compared with age-matched Wistar-Kyoto rats (WKY). Thromboxane A2 generation was also significantly enhanced by 59% in the cultured vascular smooth muscle cells of SHR when compared with production in WKY. Vascular smooth muscle cells of SHR exhibited a significantly shortened doubling time (by 32%) and greater [3H]thymidine uptake (by 56%), as compared with those of WKY. OKY 046 (10(-5) M), a thromboxane synthase inhibitor, significantly tempered the rapid vascular smooth muscle cell growth in SHR by 9% for doubling time and by 10% for [3H]thymidine uptake. OKY 046 did not influence the doubling time of WKY. Conversely, a stable analogue of thromboxane A2 dose-dependently stimulated the [3H]thymidine uptake by vascular smooth muscle cells of WKY, and, at a concentration of 10(-5) M, shortened the doubling time of vascular smooth muscle cells of WKY by 11%, whereas it showed slight effects on SHR. These data indicate that vascular thromboxane A2 is involved in the regulatory mechanism of vascular smooth muscle cell growth and that enhanced vascular thromboxane A2 generation is partly responsible for the rapid proliferation of vascular smooth muscle cells of SHR. The alterations of vascular thromboxane production may be a key trait for genetic hypertension.
血管壁具有产生血栓素A2的能力。然而，血管血栓素A2的作用仍不明确。在本研究中，我们检测了自发性高血压大鼠（SHR）血管血栓素A2生成与血管平滑肌细胞生长之间的关系。与年龄匹配的Wistar-Kyoto大鼠（WKY）相比，5周龄SHR的血管血栓素A2生成显著增加49%，15周龄SHR则增加117%。与WKY相比，SHR培养的血管平滑肌细胞中血栓素A2生成也显著增加59%。与WKY相比，SHR的血管平滑肌细胞倍增时间显著缩短（32%），[3H]胸苷摄取量更高（56%）。血栓素合酶抑制剂OKY 046（10^(-5) M）显著抑制SHR血管平滑肌细胞的快速生长，使倍增时间延长9%，[3H]胸苷摄取量降低10%。OKY 046对WKY的倍增时间没有影响。相反，血栓素A2的稳定类似物剂量依赖性地刺激WKY血管平滑肌细胞的[3H]胸苷摄取，在浓度为10^(-5) M时，使WKY血管平滑肌细胞的倍增时间缩短11%，而对SHR的影响较小。这些数据表明，血管血栓素A2参与血管平滑肌细胞生长的调节机制，血管血栓素A2生成增加是SHR血管平滑肌细胞快速增殖的部分原因。血管血栓素生成的改变可能是遗传性高血压的一个关键特征。
