ESTROGEN AND SIMVASTATIN EFFECT OF NITRIC OXIDE BIOACTIVITY AND INFLAMMATION

在动物模型和人类中的动脉粥样硬化是 与炎症有关。增加一氧化氮的疗法 生物活性减少促炎蛋白的合成， 通过抑制靶基因的转录激活来抑制血管壁。 由于雌激素和降脂疗法已被证明 为了提高一氧化氮生物活性，我们给予了结合马 雌激素0.625 mg，辛伐他汀10 mg或联合用药，每日6次 28周高胆固醇血症（低密度脂蛋白= 163+/-36 mg/dL;平均值+/- SD）， 随机、双盲、双交叉研究。我们测量 前臂缺血后肱动脉血流介导的扩张， 和炎性细胞粘附分子E-选择素，细胞间 粘附分子-1与血管细胞粘附 分子（VCAM-1）。单独的结合雌激素降低了 E-选择素降低17+/-14%（p<.001），ICAM-1降低3+/-23%， VCAM-1较各自预处理降低14+/-21%（p<.01） 价值观结合雌激素联合辛伐他汀也 这些细胞粘附分子的水平降低; E-选择素， 18+/-16%，ICAM-1 8+/-15%，VCAM-1 12+/-19%， 各自的预处理值（所有p<.01）。然而，辛伐他汀 单独使用没有改变E-选择素（+6+/-3%）、ICAM-1 （+5+/-27%）或VCAM-1（-3+/-26%） 价值观血流介导的显著和等效改善 每种治疗均观察到扩张：结合雌激素4.0+/-2.6 至10.2+/-3.9%，辛伐他汀4.3+/-2.4至10.0+/-3.9%，结合 雌激素加辛伐他汀4.6+/-2.0至9.8+/-2.6%（所有P<0.001 相对于各自的治疗前基线值）。但只有 包括结合雌激素在内的疗法降低了细胞水平， 粘附分子因此，提高一氧化氮水平的疗法 生物活性可能对抗炎作用不具有可比性 潜力

Atherosclerosis in animal models and in humans is associated with inflammation. Therapies that increase nitric oxide bioactivity reduce synthesis of proinflammatory proteins within the vessel wall by inhibiting transcriptional activation of target genes. As estrogen and lipid-lowering therapies have been shown to improve nitric oxide bioactivity, we administered conjugated equine estrogen .625 mg, simvastatin 10 mg or the combination daily for 6 weeks to 28 hypercholesterolemic (low density lipoprotein = 163+/-36 mg/dL;mean +/- SD) postmenopausal women in a randomized, double blind, double-crossover study. We measured brachial artery flow-mediated dilation following forearm ischemia, and inflammatory cell adhesion molecules E-selectin, intercellular adhesion molecule (ICAM-1) and the vascular cell adhesion molecule (VCAM-1). Conjugated estrogen alone reduced levels of E-selectin by 17+/-14% (p<.001), ICAM-1 by 3+/-23% and VCAM-1 by 14+/-21%(p<.01) from respective pretreatment values. Conjugated estrogen combined with simvastatin also reduced levels of these cell adhesion molecules; E-selectin by 18+/-16%, ICAM-1 by 8+/-15% and VCAM-1 by 12+/-19% from respective pretreatment values (all p<.01). However, simvastatin alone did not change levels of E-selectin (+6+/-3%), ICAM-1 (+5+/-27%), or VCAM-1 (-3+/-26%) from respective pretreatment values. Significant and equivalent improvement in flow-mediated dilation was seen with each therapy: conjugated estrogen 4.0+/-2.6 to 10.2+/-3.9%, simvastatin 4.3+/-2.4 to 10.0+/-3.9%, conjugated estrogen plus simvastatin 4.6+/-2.0 to 9.8+/-2.6% (all p<.001 versus respective pretreatment baseline values). However, only therapies including conjugated estrogen reduced levels of cell adhesion molecules. Thus, therapies that improve nitric oxide bioactivity may not have comparable effects on anti-inflammatory potential.