Davidge S T, Baker P N, Laughlin M K, Roberts J M
Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh, Pa, USA.
Circ Res. 1995 Aug;77(2):274-83. doi: 10.1161/01.res.77.2.274.
The endothelium serves many functional roles, including the modulation of vascular smooth muscle tone through the release of vasoactive agents such as nitric oxide (NO) and the eicosanoids. We proposed that NO produced by endothelial cells would increase the production of eicosanoids through enhanced expression and/or activation of prostaglandin H synthase. NO and eicosanoid synthesis were stimulated in a bovine coronary microvessel endothelial cell line with the calcium ionophore A23187 (1 mumol/L). Our data demonstrated the following: (1) A23187 stimulated NO synthesis along with prostacyclin and thromboxane production. (2) Inhibition of NO synthesis with NG-nitro-L-arginine methyl ester (0.1 mmol/L) significantly diminished both prostacyclin and thromboxane production. (3) Cells incubated with hemoglobin (2 micrograms/mL), which inactivates NO, decreased A23187-stimulated prostacyclin production, whereas cells incubated with superoxide dismutase (20 U/mL), which protects NO from superoxide anions, enhanced prostacyclin production. (4) Exogenous NO stimulated prostacyclin production. (5) The interaction of NO with prostacyclin persisted in the presence of excess exogenous arachidonic acid (100 mumol/L). (6) Cyclooxygenase activity in cell lysates increased in the first hour of NO stimulation. (7) NO stimulation of prostacyclin occurred within 1 hour and continued for 8 hours. (8) Neither constitutive nor inducible prostaglandin H synthase enzyme expression was altered by NO. (9) Cycloheximide (10 mumol/L) had no effect on A23187 stimulation of prostacyclin production. (10) Exogenous cGMP (10 mumol/L) or a phosphodiesterase inhibitor (1 mmol/L) did not affect prostacyclin production. These data indicate that stimulating synthesis of endogenous NO in cultured endothelial cells increased eicosanoid production through activation of prostaglandin H synthase.
内皮细胞具有多种功能作用，包括通过释放一氧化氮（NO）和类花生酸等血管活性物质来调节血管平滑肌张力。我们提出，内皮细胞产生的NO会通过增强前列腺素H合酶的表达和/或激活来增加类花生酸的生成。用钙离子载体A23187（1 μmol/L）刺激牛冠状动脉微血管内皮细胞系中的NO和类花生酸合成。我们的数据表明：（1）A23187刺激NO合成以及前列环素和血栓素的生成。（2）用NG-硝基-L-精氨酸甲酯（0.1 mmol/L）抑制NO合成可显著减少前列环素和血栓素的生成。（3）用可使NO失活的血红蛋白（2 μg/mL）孵育细胞，可降低A23187刺激的前列环素生成，而用可保护NO免受超氧阴离子影响的超氧化物歧化酶（20 U/mL）孵育细胞，则可增强前列环素生成。（4）外源性NO刺激前列环素生成。（5）在存在过量外源性花生四烯酸（100 μmol/L）的情况下，NO与前列环素的相互作用仍然存在。（6）在NO刺激的第一小时内，细胞裂解物中的环氧化酶活性增加。（7）NO对前列环素的刺激在1小时内发生并持续8小时。（8）NO既不改变组成型也不改变诱导型前列腺素H合酶的酶表达。（9）环己酰亚胺（10 μmol/L）对A23187刺激的前列环素生成没有影响。（10）外源性环鸟苷酸（10 μmol/L）或磷酸二酯酶抑制剂（1 mmol/L）不影响前列环素生成。这些数据表明，刺激培养的内皮细胞中内源性NO的合成可通过激活前列腺素H合酶增加类花生酸的生成。
