Brown Nancy J, Kumar Sandeep, Painter Corrie A, Vaughan Douglas E
Division of Clinical Pharmacology, Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232-6602, USA.
Hypertension. 2002 Dec;40(6):859-65. doi: 10.1161/01.hyp.0000040264.15961.48.
ACE inhibition reduces plasminogen activator inhibitor-1 (PAI-1), a risk factor for myocardial infarction, whereas the effect of angiotensin receptor antagonism on PAI-1 is uncertain. The present study compares the time course of effects of ACE inhibition and angiotensin type 1 (AT1) receptor antagonism on morning plasma PAI-1 antigen. Blood pressure and endocrine, metabolic, and fibrinolytic variables were measured in 20 insulin-resistant (defined by fasting glucose >8.3 mmol/L, body mass index >28 kg/m2, or fasting serum triglyceride > or =2.8 mmol/L) hypertensive subjects (mean age, 47.9+/-2.1 years) (1) before and after 1 week of hydrochlorothiazide 12.5 mg/d, and (2) before and 1, 3, 4, and 6 weeks after addition of ramipril (escalated to 10 mg/d) or losartan (escalated to 100 mg/d). Hydrochlorothiazide decreased systolic (P=0.011) and diastolic (P=0.019) pressure. Ramipril (from 133.6+/-5.1/94.5+/-2.4 to 127.0+/-3.1/91.4+/-3.3 mm Hg) or losartan (from 137.0+/-3.9/93.1+/-2.9 to 123.7+/-2.6/86.4+/-2.1 mm Hg) further reduced systolic (P=0.009) and diastolic (P=0.037) pressure. The pressure effects of the 2 drugs were similar. Hydrochlorothiazide increased plasma PAI-1 (P=0.013) but not tissue-type plasminogen activator (tPA) (P=0.431) antigen. Addition of either ramipril or losartan significantly decreased plasma PAI-1 antigen (P=0.046). However, the effect of losartan on PAI-1 antigen was not sustained throughout the 6-week treatment period, such that there was a significant drugxtime interaction (P=0.043). tPA antigen decreased during either ramipril or losartan (P=0.032), but tPA activity decreased only during losartan (P=0.018). Short-term interruption of the renin-angiotensin-aldosterone system by either ACE inhibition or AT1 receptor antagonism decreases PAI-1 antigen, but the duration of this effect is greater for ACE inhibition than for AT1 receptor antagonism.
血管紧张素转换酶（ACE）抑制可降低纤溶酶原激活物抑制剂-1（PAI-1），PAI-1是心肌梗死的一个危险因素，而血管紧张素受体拮抗剂对PAI-1的影响尚不确定。本研究比较了ACE抑制和1型血管紧张素（AT1）受体拮抗对早晨血浆PAI-1抗原的作用时间过程。对20名胰岛素抵抗（定义为空腹血糖>8.3 mmol/L、体重指数>28 kg/m2或空腹血清甘油三酯>或=2.8 mmol/L）的高血压患者（平均年龄47.9±2.1岁）进行血压及内分泌、代谢和纤溶变量的测量：（1）在服用12.5 mg/d氢氯噻嗪1周前后；（2）在加用雷米普利（剂量递增至10 mg/d）或氯沙坦（剂量递增至100 mg/d）前及用药后1、3、4和6周。氢氯噻嗪降低了收缩压（P=0.011）和舒张压（P=0.019）。雷米普利（从133.6±5.1/94.5±2.4降至127.0±3.1/91.4±3.3 mmHg）或氯沙坦（从137.0±3.9/93.1±2.9降至123.7±2.6/86.4±2.1 mmHg）进一步降低了收缩压（P=0.009）和舒张压（P=0.037）。两种药物的降压效果相似。氢氯噻嗪增加了血浆PAI-1（P=0.013），但未增加组织型纤溶酶原激活物（tPA）抗原（P=0.431）。加用雷米普利或氯沙坦均可显著降低血浆PAI-1抗原（P=0.046）。然而，氯沙坦对PAI-1抗原的作用在6周治疗期内未持续，存在显著的药物×时间交互作用（P=0.043）。雷米普利或氯沙坦治疗期间tPA抗原均降低（P=0.032），但仅氯沙坦治疗期间tPA活性降低（P=0.018）。通过ACE抑制或AT1受体拮抗短期阻断肾素-血管紧张素-醛固酮系统可降低PAI-1抗原，但ACE抑制这种作用的持续时间比AT1受体拮抗更长。
