Pretorius Mias, van Guilder Gary P, Guzman Raul J, Luther James M, Brown Nancy J
Department of Anesthesiology, Vanderbilt University School of Medicine, Nashville, Tenn., USA.
Hypertension. 2008 Apr;51(4):1190-6. doi: 10.1161/HYPERTENSIONAHA.107.105627. Epub 2008 Feb 7.
Angiotensin-converting enzyme inhibition potentiates basal and bradykinin-stimulated tissue-type plasminogen activator (t-PA) release to a greater extent in women than in men. This study tested the hypothesis that 17beta-estradiol enhances the effect of angiotensin-converting enzyme inhibition on t-PA release in young postmenopausal women. We conducted a double-blind, prospective, crossover study in 14 young postmenopausal women (mean age 48.2+/-2.3 years) who were randomized to receive 17beta-estradiol (1 mg/d) or matching placebo for 4 weeks. At the end of each treatment period, we measured the effect of intraarterial infusion of bradykinin, methacholine, and nitroprusside on forearm blood flow and net t-PA release, before and during intraarterial enalaprilat (0.33 microg/min/100 mL forearm volume). 17Beta-estradiol significantly reduced baseline venous plasminogen activator inhibitor-1 antigen (4.4+/-1.4 versus 10.4+/-2.5 ng/mL, P=0.001) and t-PA antigen (5.5+/-0.6 versus 7.5+/-1.3 ng/mL, P=0.022) compared with placebo. 17Beta-estradiol increased basal forearm vascular release of active t-PA compared with placebo (1.2+/-0.3 IU/mL/min versus 0.4+/-0.1 IU/mL/min respectively, P=0.032), without increasing t-PA antigen release (P=0.761). Enalaprilat significantly increased basal net t-PA antigen release (from -0.8+/-1.0 to 3.2+/-1.2 ng/min/100 mL, P=0.012), but not the release of active t-PA, during either placebo or 17beta-estradiol. Enalaprilat potentiated bradykinin-stimulated vasodilation and t-PA antigen and activity release similarly during placebo and 17beta-estradiol treatment. 17Beta-estradiol treatment does not alter the effect of angiotensin-converting enzyme inhibition on basal t-PA antigen or on bradykinin-stimulated t-PA antigen or activity release. 17Beta-estradiol increases basal release of active t-PA in young postmenopausal women, consistent with enhanced vascular fibrinolytic function.
与男性相比，血管紧张素转换酶抑制作用在女性中能更大程度地增强基础状态下和缓激肽刺激的组织型纤溶酶原激活物（t-PA）释放。本研究检验了这样一个假设：17β-雌二醇可增强血管紧张素转换酶抑制作用对年轻绝经后女性t-PA释放的影响。我们对14名年轻绝经后女性（平均年龄48.2±2.3岁）进行了一项双盲、前瞻性、交叉研究，这些女性被随机分为接受17β-雌二醇（1mg/d）或匹配的安慰剂治疗4周。在每个治疗期结束时，我们测量了动脉内输注缓激肽、乙酰甲胆碱和硝普钠对前臂血流量和净t-PA释放的影响，分别在动脉内输注依那普利拉（0.33μg/min/100mL前臂容积）之前和期间进行测量。与安慰剂相比，17β-雌二醇显著降低了基线静脉纤溶酶原激活物抑制剂-1抗原水平（4.4±1.4对10.4±2.5ng/mL，P=0.001）和t-PA抗原水平（5.5±0.6对7.5±1.3ng/mL，P=0.022）。与安慰剂相比，17β-雌二醇增加了基础状态下前臂血管活性t-PA的释放（分别为1.2±0.3IU/mL/min对0.4±0.1IU/mL/min，P=0.032），而未增加t-PA抗原的释放（P=0.761）。在安慰剂或17β-雌二醇治疗期间，依那普利拉显著增加了基础状态下净t-PA抗原的释放（从-0.8±1.0至3.2±1.2ng/min/100mL，P=0.012），但未增加活性t-PA的释放。在安慰剂和17β-雌二醇治疗期间，依那普利拉对缓激肽刺激的血管舒张以及t-PA抗原和活性释放的增强作用相似。17β-雌二醇治疗不会改变血管紧张素转换酶抑制作用对基础t-PA抗原或缓激肽刺激的t-PA抗原或活性释放的影响。17β-雌二醇增加了年轻绝经后女性基础状态下活性t-PA的释放，这与增强的血管纤溶功能一致。
