Zancan V, Santagati S, Bolego C, Vegeto E, Maggi A, Puglisi L
Institute of Pharmacological Sciences, University of Milan, Italy.
Endocrinology. 1999 May;140(5):2004-9. doi: 10.1210/endo.140.5.6694.
Several studies have provided evidence for a direct effect of 17beta-estradiol on vessel wall via interaction with the constitutively expressed nitric oxide synthase (NOS) by endothelium. The aim of the present study was to investigate the effect of 17beta-estradiol on inducible NOS (NOS II) in primary culture of smooth muscle cells (SMC) from rat aorta. We here prove that 17beta-estradiol decreases the content and activity of NOS II in SMC. This effect appears to be the consequence of ER activation, because: 1) ER alpha and ER beta are expressed in rat aorta SMC grown in culture; 2) low concentrations of hormone modulate NOS II activity; 3) the specific ER alpha antagonist ICI182,780 completely blocks 17beta-estradiol effect. On the other hand, progesterone is deprived of any effect on NOS II content or activity, proving the specificity of 17beta-estradiol effect. In addition, we show that 17beta-estradiol can counteract the increase in NOS II activity following cytokine treatment. The observation could indicate a novel mechanism for the protective effects exerted by these hormones in cardiovascular diseases and atherosclerosis in particular.
多项研究已提供证据，表明17β-雌二醇可通过与内皮细胞持续表达的一氧化氮合酶（NOS）相互作用，直接作用于血管壁。本研究的目的是探讨17β-雌二醇对大鼠主动脉平滑肌细胞（SMC）原代培养中诱导型NOS（NOS II）的影响。我们在此证明，17β-雌二醇可降低SMC中NOS II的含量和活性。这种作用似乎是雌激素受体（ER）激活的结果，因为：1）ERα和ERβ在培养的大鼠主动脉SMC中表达；2）低浓度的激素可调节NOS II的活性；3）特异性ERα拮抗剂ICI182,780可完全阻断17β-雌二醇的作用。另一方面，孕酮对NOS II的含量或活性没有任何影响，这证明了17β-雌二醇作用的特异性。此外，我们表明17β-雌二醇可抵消细胞因子处理后NOS II活性的增加。这一观察结果可能表明这些激素在心血管疾病尤其是动脉粥样硬化中发挥保护作用的一种新机制。
