Brown N J, Agirbasli M A, Williams G H, Litchfield W R, Vaughan D E
Departments of Medicine and Pharmacology, Vanderbilt University Medical Center, Nashville, Tenn 37232-6602, USA.
Hypertension. 1998 Dec;32(6):965-71. doi: 10.1161/01.hyp.32.6.965.
Increased plasma renin activity (PRA) has been associated with an increased risk of myocardial infarction (MI), whereas angiotensin-converting enzyme (ACE) inhibition appears to reduce the risk of recurrent MI in patients with left ventricular dysfunction. These observations may be partially explained by an interaction between the renin-angiotensin system (RAS) and fibrinolytic system. To test this hypothesis, we examined the effect of salt depletion on tissue-type plasminogen activator (tPA) antigen and plasminogen activator inhibitor-1 (PAI-1) activity and antigen in normotensive subjects in the presence and absence of quinapril (40 mg BID). Under low (10 mmol/d) and high (200 mmol/d) salt conditions there was significant diurnal variation in PAI-1 antigen and activity and tPA antigen. Morning (8 AM through 2 PM) PAI-1 antigen levels were significantly higher during low salt intake compared with high salt intake conditions (ANOVA, F=5.8, P=0.048). PAI-1 antigen correlated with aldosterone (r=0.56, P<10(-7)) during low salt intake. ACE inhibition significantly decreased 24-hour (ANOVA for 24 hours, F=6. 7, P=0.04) and morning (F=24, P=0.002) PAI-1 antigen and PAI-1 activity (F=6.48, P=0.038) but did not alter tPA antigen. Thus, the mean morning PAI-1 antigen concentration was significantly higher during low salt intake than during either high salt intake or low salt intake and concomitant ACE inhibition (22.7+/-4.6 versus 16. 1+/-3.3 and 16.3+/-3.7 ng/mL, respectively; P<0.05). This study provides evidence of a direct functional link between the RAS and fibrinolytic system in humans. The data suggest that ACE inhibition has the potential to reduce the incidence of thrombotic cardiovascular events by blunting the morning peak in PAI-1.
血浆肾素活性（PRA）升高与心肌梗死（MI）风险增加相关，而血管紧张素转换酶（ACE）抑制似乎可降低左心室功能不全患者复发性MI的风险。这些观察结果可能部分由肾素-血管紧张素系统（RAS）与纤溶系统之间的相互作用来解释。为了验证这一假设，我们在有或无喹那普利（40mg，每日两次）的情况下，研究了盐耗竭对血压正常受试者组织型纤溶酶原激活物（tPA）抗原以及纤溶酶原激活物抑制剂-1（PAI-1）活性和抗原的影响。在低盐（10mmol/d）和高盐（200mmol/d）条件下，PAI-1抗原和活性以及tPA抗原存在显著的昼夜变化。与高盐摄入条件相比，低盐摄入期间早晨（上午8点至下午2点）的PAI-1抗原水平显著更高（方差分析，F = 5.8，P = 0.048）。低盐摄入期间，PAI-1抗原与醛固酮相关（r = 0.56，P < 10⁻⁷）。ACE抑制显著降低了24小时（24小时方差分析，F = 6.7，P = 0.04）和早晨（F = 24，P = 0.002）的PAI-1抗原和PAI-1活性（F = 6.48，P = 0.038），但未改变tPA抗原。因此，低盐摄入期间早晨PAI-1抗原的平均浓度显著高于高盐摄入期间或低盐摄入并同时进行ACE抑制的期间（分别为22.7±4.6与16.1±3.3和16.3±3.7ng/mL；P < 0.05）。本研究提供了人类RAS与纤溶系统之间直接功能联系的证据。数据表明，ACE抑制有可能通过减弱PAI-1的早晨峰值来降低血栓性心血管事件的发生率。
