Ishimitsu T, Uehara Y, Ishii M, Matsukoa H, Ikeda T, Sugimoto T
Department of Medicine, University of Tokyo, Japan.
Jpn Circ J. 1990 Dec;54(12):1546-53. doi: 10.1253/jcj.54.12_1546.
We designed experiments to investigate the roles of endogenous prostaglandins (PG) for the rapid proliferation of vascular smooth muscle cells (VSMC) of spontaneously hypertensive rats (SHR). Both the basal and arachidonate-stimulated vasodepressor PG generations were significantly enhanced in the VSMC of SHR when they were at the 1st or 2nd passage. Conversely, the generating capacity was significantly lowered in the VSMC of SHR when the cells reached the 4th or older generation. Based on the (3H)thymidine uptake and doubling time of VSMC, the decline of PG generating capacity seen in the VSMC of SHR was markedly associated with the increased VSMC growth. Indeed, the stimulation of endogenous vasodepressor PG by arachidonate produced a decrease in (3H)thymidine uptake in the VSMC of Wistar-Kyoto rats, whereas the dose was not sufficient to retard the uptake in SHR. On the other hand, the PG synthesis inhibition by indomethacin, a cyclooxygenase inhibitor, significantly enhanced the uptake by the VSMC of SHR. Thus, these data indicate that the impaired vasodepressor PG system is at least partly responsible for the rapid VSMC growth in SHR.
我们设计了实验来研究内源性前列腺素（PG）在自发性高血压大鼠（SHR）血管平滑肌细胞（VSMC）快速增殖中的作用。当SHR的VSMC处于第1代或第2代时，基础和花生四烯酸刺激的血管舒张性PG生成均显著增强。相反，当细胞达到第4代或更老一代时，SHR的VSMC中PG生成能力显著降低。基于VSMC的（3H）胸腺嘧啶核苷摄取和倍增时间，SHR的VSMC中PG生成能力的下降与VSMC生长增加显著相关。事实上，花生四烯酸对内源性血管舒张性PG的刺激导致Wistar-Kyoto大鼠VSMC中（3H）胸腺嘧啶核苷摄取减少，而该剂量不足以抑制SHR中的摄取。另一方面，环氧化酶抑制剂吲哚美辛对PG合成的抑制显著增强了SHR的VSMC的摄取。因此，这些数据表明，血管舒张性PG系统受损至少部分导致了SHR中VSMC的快速生长。
