Wang H, Mizuno R, Ohhashi T
1st Department of Physiology, Shinshu University School of Medicine, Matsumoto, Japan.
Can J Physiol Pharmacol. 1997 Jul;75(7):789-95.
We have studied mechanisms of vasodilation induced by supernatant fluid of rat macrophages (Mø), using an arterial bioassay preparation. The cells emigrated by an intraperitoneal injection of thioglycollate were isolated and cultured for 12 h in RPMI 1640 medium with and without 2.0 mM L-arginine. More than 98% of the isolated cells clearly demonstrated Wright's esterase staining and phagocytosis of acetylated low-density lipoprotein. The bioassay preparation was made of dog isolated femoral arteries with and without the endothelium. The supernatant of macrophages cultured in the L-arginine-free RPMI 1640 caused a significant reduction of the precontraction in the bioassay rings, being approximately 51.6-66.7% of sodium nitroprusside (SNP) induced maximum vasodilation in each ring. The supernatant of macrophages cultured in the RPMI 1640 containing 2.0 mM L-arginine produced a significantly smaller relaxation (approximately 32.3-33.3%). The Mø-induced vasodilation was significantly inhibited by the coculture of the macrophages with 1 microM dexamethasone, 10 microM cycloheximide, 50 microM N omega-nitro-L-arginine methyl ester (L-NAME), 10 microM indomethacin, or 10 microM aspirin. The L-NAME-induced inhibition was significantly reversed by an additional treatment with 100 microM L-arginine. The coculture with both L-NAME and indomethacin caused a reduction of the Mø-induced vasodilation (approximately 12.5-13.4%) similar to reductions produced by dexamethasone (approximately 10.8-12.1%) and cycloheximide (approximately 11.4-12.4%). Coculture with 10 micrograms/mL bacterial lipopolysaccharide caused a slight facilitation of the Mø-induced vasodilation (approximately 78.2-79.6%). These findings suggest that supernatant fluid of rat exuded macrophages cultured with low concentrations of L-arginine causes an endogenous nitric oxide (NO) and vasodilative prostaglandin dependent relaxation of arterial smooth muscles.
我们使用动脉生物测定制剂，研究了大鼠巨噬细胞（Mø）上清液诱导血管舒张的机制。通过腹腔注射巯基乙酸盐迁移出的细胞被分离出来，并在含有和不含有2.0 mM L-精氨酸的RPMI 1640培养基中培养12小时。超过98%的分离细胞明显显示出瑞氏酯酶染色以及对乙酰化低密度脂蛋白的吞噬作用。生物测定制剂由有和没有内皮的犬离体股动脉制成。在不含L-精氨酸的RPMI 1640中培养的巨噬细胞上清液，导致生物测定环中的预收缩显著降低，约为硝普钠（SNP）诱导的每个环最大血管舒张的51.6 - 66.7%。在含有2.0 mM L-精氨酸的RPMI 1640中培养的巨噬细胞上清液产生的舒张作用明显较小（约32.3 - 33.3%）。巨噬细胞诱导的血管舒张被巨噬细胞与1 microM地塞米松、10 microM放线菌酮、50 microM Nω-硝基-L-精氨酸甲酯（L-NAME）、10 microM吲哚美辛或10 microM阿司匹林共培养显著抑制。L-NAME诱导的抑制作用通过额外用100 microM L-精氨酸处理而显著逆转。L-NAME和吲哚美辛共培养导致巨噬细胞诱导的血管舒张降低（约12.5 - 13.4%），类似于地塞米松（约10.8 - 12.1%）和放线菌酮（约11.4 - 12.4%）产生的降低。与10微克/毫升细菌脂多糖共培养导致巨噬细胞诱导的血管舒张略有增强（约78.2 - 79.6%）。这些发现表明，用低浓度L-精氨酸培养的大鼠渗出巨噬细胞的上清液，会引起内源性一氧化氮（NO）和血管舒张性前列腺素依赖性的动脉平滑肌舒张。
