ESTROGEN AND SIMVASTATIN EFFECT OF NITRIC OXIDE BIOACTIVITY AND INFLAMMATION

动物模型和人类的动脉粥样硬化 与炎症有关。增加一氧化氮的治疗方法 生物活性减少体内促炎蛋白的合成 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可以 提高一氧化氮生物活性，我们给马匹注射了结合体 雌激素.625毫克，辛伐他汀10毫克或联合用药每日6次 周至28周高胆固醇血症(低密度脂蛋白= 163+/-36 mg/dL；平均值+/-SD)绝经后妇女 随机、双盲、双交叉研究。我们测量了 前臂缺血后的肱动脉血流介导的扩张， 和炎性细胞黏附分子E-选择素，细胞间 黏附分子ICAM-1与血管细胞黏附 分子(VCAM-1)。单用结合雌激素可降低 E-选择素下降17+/-14%(p&lt；.001)，ICAM-1下降3+/-23% VCAM-1比各自的处理前降低了14+/-21%(p&lt；.01) 价值观。结合雌激素联合辛伐他汀也 这些细胞黏附分子水平降低；E-选择素通过 18%+/-16%，ICAM-1增长8+/-15%，VCAM-1增长12+/-19% 各自的预处理值(所有p&lt；.01)。然而，辛伐他汀 单独应用不改变E-选择素(+6+/-3%)、ICAM-1水平 (+5+/-27%)或VCAM-1(-3+/-26%) 价值观。流中介的显著和同等改进 每种治疗方法均可见扩张：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%(P&lt；.001 与各自的处理基准值相比)。然而，只有 包括结合雌激素在内的治疗降低细胞水平 黏附分子。因此，改善一氧化氮的疗法 生物活性在抗炎方面可能没有可比的效果 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.