Nagano K, Toba K, Akishita M, Watanabe T, Kozaki K, Eto M, Hashimoto M, Sudoh N, Ako J, Yoshizumi M, Ouchi Y
Department of Geriatric Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan.
Eur J Pharmacol. 2000 Feb 11;389(1):25-33. doi: 10.1016/s0014-2999(99)00873-0.
The aim of the present study was to investigate the effect of arginine [Arg(8)]vasopressin (vasopressin) on proliferation of vascular smooth muscle cells and the mechanisms underlying the action of vasopressin. To clarify these issues, we used two different types of vascular smooth muscle cells, cultured adult rat aortic smooth muscle cells and A10 cells, a cell line derived from fetal rat aorta. Vasopressin (10(-8) to 10(-6) M) significantly stimulated the proliferation of rat aortic smooth muscle cells in a dose-dependent manner. In contrast, vasopressin significantly inhibited the proliferation of A10 cells. This inhibition was abolished when A10 cells were treated with indomethacin. Vasopressin stimulated the production of prostanoids several-fold in A10 cells but not in rat aortic smooth muscle cells. These effects were completely blocked by the vasopressin V(1) receptor antagonist, 1-¿1-[4-(3-acetylamino-propoxy)benzoyl]4-piperidyl¿-3, 4-dihydro-2(1H)-quinolinone (OPC21268), but not by the vasopressin V(2) receptor antagonist, (+/-)-5-dimethylamino-1-[4-(2-methylbenzoylamino)benzol]-2, 3,4,5-tetrahydro-1H-benzazepine hydrochloride (OPC31260). These results indicate that vasopressin has diverse effect on proliferation of vascular smooth muscle cells through the vasopressin V(1) receptor, depending on the production of growth regulatory prostanoids.
本研究的目的是探讨精氨酸[Arg(8)]加压素(加压素)对血管平滑肌细胞增殖的影响以及加压素作用的潜在机制。为阐明这些问题,我们使用了两种不同类型的血管平滑肌细胞,即培养的成年大鼠主动脉平滑肌细胞和A10细胞(一种源自胎鼠主动脉的细胞系)。加压素(10^(-8)至10^(-6) M)以剂量依赖的方式显著刺激大鼠主动脉平滑肌细胞的增殖。相反,加压素显著抑制A10细胞的增殖。当用吲哚美辛处理A10细胞时,这种抑制作用被消除。加压素在A10细胞中刺激前列腺素的产生增加了几倍,但在大鼠主动脉平滑肌细胞中没有。这些作用被加压素V(1)受体拮抗剂1-{1-[4-(3-乙酰氨基-丙氧基)苯甲酰基]-4-哌啶基}-3,4-二氢-2(1H)-喹啉酮(OPC21268)完全阻断,但未被加压素V(2)受体拮抗剂(+/-)-5-二甲基氨基-1-[4-(2-甲基苯甲酰氨基)苯]-2,3,4,5-四氢-1H-苯并氮杂卓盐酸盐(OPC31260)阻断。这些结果表明,加压素通过加压素V(1)受体对血管平滑肌细胞的增殖具有不同的作用,这取决于生长调节前列腺素的产生。