Ikeda U, Murakami Y, Kanbe T, Shimada K
Department of Cardiology, Jichi Medical School, Tochigi, Japan.
J Mol Cell Cardiol. 1996 Jul;28(7):1539-45. doi: 10.1006/jmcc.1996.0144.
We investigated the effects of alpha 1-adrenergic stimulation on nitric oxide (NO) production by cardiac myocytes. Incubation of cultured neonatal rat cardiac myocytes with interleukin-1 beta (IL-1 beta) caused a significant increase in the production of nitrite, a stable metabolite of NO. Addition of phenylephrine significantly augmented nitrite production by IL-1 beta-stimulated but not by unstimulated myocytes in a dose-dependent manner. The effect of phenylephrine was completely abolished in the presence of NG-monomethyl-L-arginine (L-NMMA) or actinomycin D. Northern blotting revealed increased inducible NO synthase mRNA accumulation in cardiac myocytes treated with IL-1 beta and phenylephrine compared with those treated with IL-1 beta alone. After protein kinase C activity was functionally depleted by treating cells with phorbol 12-myristate 13-acetate for 24 h, phenylephrine did not augment IL-1 beta-induced NO production. The effect of phenylephrine was also abolished in the presence of protein kinase C inhibitor calphostin C. These observations suggest that alpha 1-adrenergic stimulation causes an upregulation of cytokine-induced NO production by cardiac myocytes, which is mediated at least partially via activation of protein kinase C.
我们研究了α1-肾上腺素能刺激对心肌细胞一氧化氮（NO）生成的影响。用白细胞介素-1β（IL-1β）孵育培养的新生大鼠心肌细胞会导致亚硝酸盐生成显著增加，亚硝酸盐是NO的一种稳定代谢产物。加入去氧肾上腺素以剂量依赖方式显著增强了IL-1β刺激的心肌细胞而非未刺激的心肌细胞的亚硝酸盐生成。在存在NG-单甲基-L-精氨酸（L-NMMA）或放线菌素D的情况下，去氧肾上腺素的作用完全被消除。Northern印迹分析显示，与单独用IL-1β处理的心肌细胞相比，用IL-1β和去氧肾上腺素处理的心肌细胞中诱导型一氧化氮合酶mRNA积累增加。在用佛波醇12-肉豆蔻酸酯13-乙酸酯处理细胞24小时使蛋白激酶C活性功能性耗竭后，去氧肾上腺素并未增强IL-1β诱导的NO生成。在存在蛋白激酶C抑制剂钙泊三醇C的情况下，去氧肾上腺素的作用也被消除。这些观察结果表明，α1-肾上腺素能刺激导致心肌细胞细胞因子诱导的NO生成上调，这至少部分是通过蛋白激酶C的激活介导的。
