Asbrink S, Zickert A, Bratt J, Gyllenhammar H, Palmblad J
Department of Medicine, The Center for Inflammation and Hematology Research, The Clinical Research Center, Huddinge University Hospital, S-141 86, Huddinge, Sweden.
Biochem Pharmacol. 2000 Apr 15;59(8):1007-13. doi: 10.1016/s0006-2952(99)00393-7.
Since carvedilol has been claimed to possess antioxidative effects, this drug might affect functional responses, including nitric oxide (NO) generation, of polymorphonuclear neutrophils (PMN) and macrophages. When we assessed the effects of carvedilol on PMN responses in vitro, we observed that carvedilol dose dependently modulated generation of superoxide ions by NADPH oxidase when induced by the formylpeptide formyl-methionyl-leucyl-phenylalanine (fMLP) or the phorbol ester phorbol myristate acetate. This effect was not coupled to diminished phospholipase C activity. In contrast to the effect on NADPH oxidase, neither the fMLP-elicited NO generation by PMN nor the response of the murine macrophage cell line J774 to lipopolysaccharide was affected. There was no evidence from cell-free assay systems that carvedilol is a scavenger for superoxide ions or NO. Moreover, carvedilol did not affect other reactions dependent on NO, e.g. spontaneous or fMLP-stimulated PMN migration or lipoxin A(4)-, fMLP-, or A23187-induced neutrophil cytotoxicity for human umbilical vein endothelial cells. Thus, these effects point to the possibility that carvedilol modulates the NADPH oxidase of PMN but leaves the nitric oxide synthase of phagocytes intact.
由于卡维地洛据称具有抗氧化作用，该药物可能会影响多形核中性粒细胞（PMN）和巨噬细胞的功能反应，包括一氧化氮（NO）的生成。当我们在体外评估卡维地洛对PMN反应的影响时，我们观察到，当由甲酰肽甲酰 - 甲硫氨酰 - 亮氨酰 - 苯丙氨酸（fMLP）或佛波酯佛波醇肉豆蔻酸酯乙酸盐诱导时，卡维地洛剂量依赖性地调节NADPH氧化酶产生超氧离子。这种作用与磷脂酶C活性降低无关。与对NADPH氧化酶的作用相反，PMN由fMLP诱导产生的NO以及小鼠巨噬细胞系J774对脂多糖的反应均未受影响。无细胞检测系统的证据表明卡维地洛是超氧离子或NO的清除剂。此外，卡维地洛不影响其他依赖于NO的反应，例如自发的或fMLP刺激的PMN迁移或脂氧素A(4)-、fMLP-或A23187诱导的中性粒细胞对人脐静脉内皮细胞的细胞毒性。因此，这些作用表明卡维地洛可能调节PMN的NADPH氧化酶，但使吞噬细胞的一氧化氮合酶保持完整。
