Yen Chia-Hung, Lau Ying-Tung
Department of Physiology and Pharmacology, Chang Gung University College of Medicine, 259 Wen Hwa 1 Rd., Kwei-Shan, Taoyuan, Taiwan, Republic of China.
Clin Sci (Lond). 2004 May;106(5):541-6. doi: 10.1042/CS20030334.
17beta-Oestradiol (E(2); oestrogen) is known to increase endothelium-dependent vasodilatation and NO (nitric oxide) production. It is also known to decrease the response of VSMCs (vascular smooth muscle cells) to vasoconstrictors in vitro. E(2) induces a decrease in age-related BP (blood pressure) development in MSHR (male spontaneously hypertensive rats). Whether this decrease is due to an effect on the endothelium or smooth muscle is unknown. To determine this effect, we examined the role of E(2) on vascular endothelium and smooth muscle separately. We treated MSHR with E(2) (2 mg x kg(-1) of body weight x week(-1)) for 5-7 weeks and then examined the vasoconstrictor response in the intact and denuded rings (with or without endothelium respectively). SBP (systolic BP) was measured weekly. Aortic cGMP and cAMP contents, aortic vasoconstrictor response, endothelium suppression of the vasoconstrictor response and basal NO release from aortic rings were all measured at the end of the study. We found that the age-related development of SBP in MSHR was decreased in E(2)-treated rats. The vascular response of denuded rings to a vasoconstrictor (phenylephrine and KCl) was increased in E(2)-treated rats; however, this phenomenon was masked in intact rings. The enhanced endothelial function appears to override the E(2)-increased smooth muscle vasoconstrictor response. Endothelium suppression, NO release and aortic cGMP content were all significantly higher in E(2)-treated rats than in controls. Thus our results suggest that E(2) improves endothelium function; furthermore, the accompanied NO/cGMP increase and the endothelium suppression may be associated with an E(2)-induced BP-lowering effect in MSHR.
已知17β-雌二醇（E₂；雌激素）可增强内皮依赖性血管舒张和一氧化氮（NO）生成。还已知其在体外可降低血管平滑肌细胞（VSMC）对血管收缩剂的反应。E₂可使雄性自发性高血压大鼠（MSHR）与年龄相关的血压（BP）升高减缓。这种降低是由于对内皮还是平滑肌的作用尚不清楚。为确定这种作用，我们分别研究了E₂对血管内皮和平滑肌的作用。我们用E₂（2 mg·kg⁻¹体重·周⁻¹）处理MSHR 5 - 7周，然后检测完整环和去内皮环（分别有或无内皮）的血管收缩反应。每周测量收缩压（SBP）。在研究结束时测量主动脉环的环磷酸鸟苷（cGMP）和环磷酸腺苷（cAMP）含量、主动脉血管收缩反应、内皮对血管收缩反应的抑制以及主动脉环基础NO释放。我们发现，E₂处理的大鼠中，MSHR与年龄相关的SBP升高减缓。E₂处理的大鼠中，去内皮环对血管收缩剂（去氧肾上腺素和氯化钾）的血管反应增强；然而，这种现象在完整环中被掩盖。增强的内皮功能似乎掩盖了E₂增强的平滑肌血管收缩反应。E₂处理的大鼠中，内皮抑制、NO释放和主动脉cGMP含量均显著高于对照组。因此，我们的结果表明，E₂可改善内皮功能；此外，伴随的NO/cGMP增加和内皮抑制可能与E₂诱导MSHR血压降低的作用有关。
