Yasunari K, Kohno M, Balmforth A, Murakawa K, Yokokawa K, Kurihara N, Takeda T
First Department of Internal Medicine, Osaka City University Medical School, Japan.
Hypertension. 1989 Jun;13(6 Pt 1):575-81. doi: 10.1161/01.hyp.13.6.575.
The effect of glucocorticoids on the dopamine (DA)-mediated cyclic adenosine monophosphate (cAMP) by intact vascular smooth muscle cells (VSMC) was studied in rats. Cultured VSMC were obtained from renal arteries of 14-week-old Wistar-Kyoto rats by explant method. Micromolar concentrations of dexamethasone (DEX) pretreatment for 48 hours potentiated DA-mediated response without any change of affinity constant. However, micromolar concentrations of aldosterone pretreatment for 48 hours had almost no effect on DA-mediated response. The DEX-induced facilitation began at 6 hours and reached maximum at 24 hours after DEX administration in a dose-dependent manner. Inhibitors of protein and RNA synthesis blocked this glucocorticoid effect. The basal activity of adenylate cyclase in DEX-treated cells was twofold higher than that in control cells. Treatment of VSMC with DEX increased cholera toxin-stimulated and forskolin-stimulated adenylate cyclase activity. However, pertussis toxin treatment did not augment or reduce the effect of DEX treatment. These results suggest that glucocorticoids increase DA-mediated cAMP formation by VSMC through glucocorticoid type II receptors and the induction of protein synthesis and that the activation of the catalytic unit may play some role in this facilitation.
在大鼠中研究了糖皮质激素对完整血管平滑肌细胞（VSMC）中多巴胺（DA）介导的环磷酸腺苷（cAMP）的影响。通过外植法从14周龄Wistar-Kyoto大鼠的肾动脉获取培养的VSMC。微摩尔浓度的地塞米松（DEX）预处理48小时可增强DA介导的反应，而亲和力常数无任何变化。然而，微摩尔浓度的醛固酮预处理48小时对DA介导的反应几乎没有影响。DEX诱导的促进作用在DEX给药后6小时开始，并在24小时达到最大，呈剂量依赖性。蛋白质和RNA合成抑制剂可阻断这种糖皮质激素效应。DEX处理细胞中腺苷酸环化酶的基础活性比对照细胞高两倍。用DEX处理VSMC可增加霍乱毒素刺激和福斯高林刺激的腺苷酸环化酶活性。然而，百日咳毒素处理并未增强或降低DEX处理的效果。这些结果表明，糖皮质激素通过糖皮质激素II型受体以及蛋白质合成的诱导增加VSMC中DA介导的cAMP形成，并且催化单位的激活可能在这种促进作用中发挥一定作用。
