氯沙坦和阿替洛尔对高血压患者纤溶系统及血浆血管性血友病因子的作用比较

目的比较血管紧张素受体拮抗剂(ARB)氯沙坦和β受体阻滞剂阿替洛尔对原发性高血压患者纤溶系统及血浆血管性血友病因子(vWF)的影响。方法轻中度原发性高血压患者60例随机分成氯沙坦组和阿替洛尔组(每组30例),分别给予氯沙坦50mg/(次.d)或阿替洛尔50mg/(次.d),共治疗8周。每4周随访1次,4周时血压如不达标(BP<140/90mmHg)则加用双氢克尿噻12.5mg/(次.d)。治疗前后行血浆组织型纤溶酶原激活物(tPA)及纤溶酶原激活物抑制剂1(PAI-1)检测,并计算PAI-1/tPA作为纤溶参数,同时测定血浆vWF的含量。结果两组的基线血压等一般情况具有可比性。治疗4周及8周时两组血压均较治疗前显著下降,组间比较无差异。同治疗前相比,氯沙坦组治疗8周时血浆PAI-1和vWF水平下降(P值分别<0.05及<0.01),PAI-1/tPA也有显著下降(P<0.05),而tPA则无显著变化(P>0.05);阿替洛尔组治疗8周时血浆PAI-1和vWF水平及PAI-1/tPA均无显著变化,而tPA则有所上升(P<0.05)。治疗后血浆vWF两组间比较,差异有非常显著意义。结论氯沙坦治疗能改善原发性高血压患者的纤溶系统并降低血浆vWF,而阿替洛尔则未见有此作用。     

Comparative effect of angiotensin-converting enzyme inhibition and angiotensin II type 1 receptor antagonism on plasma fibrinolytic balance in humans.

Angiotensin-converting enzyme (ACE) inhibition significantly decreases plasminogen activator inhibitor-1 (PAI-1) without altering tissue plasminogen activator (tPA) during activation of the renin-angiotensin-aldosterone system in humans. Because ACE inhibitors and angiotensin II type 1 (AT(1)) receptor antagonists differ in their effects on angiotensin II formation and bradykinin degradation, the present study compared the effect of equivalent hypotensive doses of an ACE inhibitor and AT(1) antagonist on fibrinolytic balance. Plasma PAI-1 antigen, tPA antigen, plasma renin activity, and aldosterone were measured in 25 normotensive subjects (19 white, 6 black; 14 men, 11 women; mean age 38.5+/-1.8 years; mean body mass index 25.3+/-0.7 kg/m(2)) during low salt intake alone (10 mmol Na/d), low salt intake + quinapril (40 mg PO bid), and low salt intake + losartan (50 mg PO bid). Compared with low salt alone (systolic blood pressure [BP] 118.8+/-2.2 mm Hg), both quinapril (106.3+/-2.5 mm Hg, P<0.001) and losartan (105.4+/-2. 8 mm Hg, P<0.001) reduced BP. No statistical difference was found between quinapril and losartan in their BP lowering effect. Losartan (P=0.009), but not quinapril, lowered heart rate. Both drugs significantly lowered aldosterone (P<0.001 versus low salt alone for each); however, this effect was significantly greater for quinapril than for losartan (P<0.001 for quinapril versus losartan). Treatment with quinapril, but not with losartan, was associated with a decrease in both PAI-1 antigen (P=0.03) and activity (P=0.018). PAI-1 activity was lower during treatment with quinapril than with losartan (P=0.015). The average PAI-1 antigen concentration was 13. 0+/-2.0 ng/mL during low salt alone, 10.5+/-1.6 ng/mL during quinapril treatment, and 12.3+/-2.1 ng/mL during losartan treatment. In contrast, plasma tPA antigen concentrations were reduced during treatment with losartan (P=0.03) but not with quinapril. This study provides the first evidence that ACE inhibitors and AT(1) antagonists differ in their effects on fibrinolytic balance under conditions of activation of the renin-angiotensin-aldosterone system. Further studies are needed to address the mechanism for the contrasting effects of these 2 classes of drugs on fibrinolysis and to define the clinical significance of these differences.     

Effect of the angiotensin II receptor blocker candesartan on fibrinolysis in patients with mild hypertension

Aim:  Impaired fibrinolysis is frequently observed in patients with the metabolic syndrome. Aim of the study was to examine the short-term effect of angiotensin II receptor blockade on the fibrinolytic system.
Methods:  Seventy-four patients with mild hypertension were randomly assigned to a 7-day treatment period with either 16 mg candesartan cilexetil or placebo. Several variables of the fibrinolytic system such as plasminogen activator inhibitor-1 (PAI-1) antigen and activity, tissue plasminogen activator (t-PA) antigen and activity as well as circulating t-PA/PAI-1 complexes were determined.
Results:  At baseline, the body mass index but not blood pressure was positively associated with PAI-1 antigen (r = 0.314, p < 0.01) and PAI-1 activity (r = 0.425, p < 0.01) but negatively with t-PA activity (r = −0.187, p < 0.05). A 7-day treatment with 16 mg candesartan cilexetil resulted in a significant greater reduction of diastolic blood pressure (−10.3 ± 10.8 mmHg vs.−5.8 ± 8.5 mmHg, p = 0.03). However, there was no significant effect of candesartan on all parameters of the fibrinolytic system under investigation, i.e. circulating PAI-1 antigen, PAI-1 activity, t-PA antigen, t-PA activity and t-PA/PAI-1 complexes. Furthermore, candesartan did not affect the characteristic circadian pattern of the variables of the fibrinolytic system.
Conclusion:  We conclude that short-term blockade of the angiotensin II receptor subtype 1 with candesartan does not have an impact on fibrinolysis in patients with mild hypertension.     

Hypo-fibrinolysis in patients with hypertension and elevated cholesterol

To test the hypothesis that increased blood pressure and hyperlipidaemia result in changes in the fibrinolytic system, 84 subjects with both hypertension and elevated serum cholesterol levels (the high risk group) were compared with 55 controls matched with respect to age, sex and body mass index (BMI). Plasminogen activator inhibitor (PAI-1), and tissue plasminogen activator (tPA) antigen and activity were measured before and after venous occlusion. In the high risk group, tPA activity was significantly lower both before and after venous occlusion and PAI-1 levels were significantly higher. In a multivariate analysis the triglyceride levels, diastolic blood pressure and cholesterol levels were independently associated with the PAI-1 levels. Diastolic blood pressure was independently and inversely associated with resting tPA activity. We conclude that patients with hypertension and hyperlipidaemia have a reduced activity of the fibrinolytic system, an effect which is unrelated to differences in age, sex, smoking or BMI.     

ACE inhibition versus angiotensin type 1 receptor antagonism: differential effects on PAI-1 over time

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.     

Effects of angiotensin converting enzyme and angiotensin II receptor inhibition on impaired fibrinolysis in systemic hypertension

Abnormalities in fibrinolysis have been reported in hypertension. Angiotensin converting enzyme (ACE) inhibitors have been shown to improve altered fibrinolytic balance in hypertensive patients. It has not been documented, however, whether this is due to a decrease in angiotensin II (Ang-II) generation or is a consequence of elevated local levels of bradykinin. Accordingly, the aim of this study was to determine the effects of an ACE inhibitor (perindopril) and an Ang-II receptor antagonist (losartan) on fibrinolytic kinetics.We have examined the serum levels of the plasminogen activator inhibitor type-1 (PAI-1) antigen and activity, tissue plasminogen activator (t-PA) antigen and activity, soluble thrombomodulin (sTM), and tissue factor pathway inhibitor (TFPI) before and after reaching the target blood pressure (< 140/90 mm Hg) in 13 hypertensive patients receiving perindopril (mean age 40 ± 11 years, 6 women, 7 men) and in 12 patients receiving losartan (mean age 38 ± 9 years, 6 women, 6 men). We also compared the baseline fibrinolytic activity of hypertensive patients with that of 12 normotensive control persons (mean age 40 ± 9 years, 6 women, 6 men). The mean basal plasma levels of PAI-1 antigen, PAI-1 activity, and sTM were significantly higher in the hypertensive patients than in normal controls (P < .005). The values of other analytes were similar in both groups. Increased plasma levels of PAI-1 antigen, PAI-1 activity, and sTM were reduced in patients after they were given perindopril and losartan (P < .005); the reductions in losartan-receiving group were more pronounced (P < .05). There were no significant effects on the plasma levels of t-PA antigen, t-PA activity, and TFPI in patients receiving the two therapeutic regimens (P > .05).In conclusion, chronic hypertension is associated with hypofibrinolysis. The beneficial effect of ACE inhibitors on fibrinolysis seems to be related to the blockade of Ang-II, and increased kinin activity does not appear to play a major role.     

Effect of amlodipine-atorvastatin combination on fibrinolysis in hypertensive hypercholesterolemic patients with insulin resistance

BACKGROUND: The aim of this study was to evaluate the effect of the amlodipine-atorvastatin combination on plasma tissue plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) activity in hypercholesterolemic, hypertensive patients with insulin resistance. METHODS: The study population included 45 patients, aged 41 to 70 years, with mild to moderate essential hypertension (diastolic blood pressure [BP] > or = 95 and < or = 105 mm Hg), hypercholesterolemia (total cholesterol > 200 and < 350 mg/dL), and insulin resistance (HOMA index > 2.5) After a 4-week wash-out period, they were randomized to amlodipine (5 mg) or atorvastatin (20 mg) or their combination at the same oral dosage for 12 weeks in three cross-over periods each separated by a 4-week placebo period (3 by 3 latin square design). At the end of the placebo wash-out and of each treatment period, office BP, total cholesterol, PAI-1, and t-PA activity were evaluated. RESULTS: The amlodipine-atorvastatin combination, in addition to the expected hypocholesterolemic effect, produced: 1) a greater decrease in PAI-1 activity (-10.2 U/mL, P <.01 v placebo) and an even greater increase in t-PA activity (+0.26 U/mL, P <.01 v placebo) than amlodipine (-0.5 U/mL for PAI-1, P = not significant; +0.17 U/mL for t-PA, P <.01 v placebo) and atorvastatin alone (respectively, -9.9 U/mL, P <.01 v placebo and +0.08 U/mL, P <.05 v placebo); and 2) a greater systolic BP/diastolic BP mean reduction (-22/17 mm Hg, P <.005 v placebo) than amlodipine (-18/14 mm Hg, P <.01 v placebo) and atorvastatin alone (-2.8/3.8 mm Hg, P <.05 v placebo only for diastolic BP). CONCLUSIONS: The positive effect on fibrinolytic balance and BP control observed suggests that in hypertensive, hypercholesterolemic patients with impaired fibrinolysis, the combination of amlodipine and atorvastatin could be the treatment of choice.     

Age-related effects of regular physical activity on hemostatic factors in men

Background Age-related changes in blood coagulation and fibrinolytic factors are associated with an increase in risk of thrombotic events. The purpose of this study was to assess the effects of age, regular aerobic exercise and detraining on blood coagulation and fibrinolytic factors in men. Methods Initially, 41 sedentary and 42 physically active men (20–64 years) were analyzed for plasma levels of coagulation and fibrinolytic factors. Twelve sedentary men were then subjected to 16-week aerobic exercise training and subsequent 2-week detraining. Their blood samples taken at rest were assayed for activity levels of prothrombin, coagulation factor (F) V, VII, VIII, IX, X, XI and XIII, antithrombin III, protein C and plasminogen, and for antigen levels of fibrinogen, prothrombin fragment 1 + 2 (F1 + 2), FIX, protein C, tissue-type plasminogen activator (tPA), plasminogen activator inhibitor 1 (PAI-1) and tPA/PAI-1 complex. Results Plasma levels of most coagulation factors, particularly for fibrinogen and FIX antigens as well as FXIII activity significantly increased with aging in sedentary men, while that tendency disappeared in physically active men. By the exercise training, plasma antigen and/or activity levels of most blood coagulation factors except for prothrombin and FIX decreased. These training-effects, however, disappeared after detraining, and in some cases even rebounded to higher levels than those of pre-training. Plasma antigen levels of tPA, PAI-1 and tPA/PAI-1 complex decreased with the training and remained low even after detraining. Conclusion Regular aerobic exercises give complex effects on expression of hemostatic factors, overall favoring the hemostatic balance to less thrombotic, partly cancelling out the age effects.     

氯沙坦对原发性高血压患者纤溶功能的影响

目的观察氯沙坦对原发性高血压(EH)患者纤溶功能的影响。方法观察34例EH患者应用氯沙坦治疗4周后收缩压(SBP)、舒张压(DBP)、心率、血浆组织型纤溶酶原激活物(t-PA)、内皮细胞型纤溶酶原激活物抑制剂(PAI-1)水平的变化,并与30例健康人作比较。结果治疗前EH患者血浆t-PA水平明显低于对照组,而PAI-1水平明显高于对照组(均P<0.01)。氯沙坦治疗4周后,血压明显下降,心率无明显变化,血浆t-PA水平增加,但无统计学意义,而PAI-1水平明显降低,t-PA/PAI-1比值升高(均P<0.01)。结论EH患者存在着内源性纤溶功能紊乱,氯沙坦可以改善EH患者的纤溶功能。     

Plasminogen Activator Inhibitor Type-1 (Part One): Basic Mechanisms,Regulation, and Role for Thromboembolic Disease

Plasminogen activator inhibitor type-1 (PAI-1) is a rapid inhibitor of tissue plasminogen activator (tPA) in circulation. Evidence suggests that the PAI-1 concentration is responsible for the regulation of the endogenous fibrinolytic system through its tPA/PAI-1 interactions. Accordingly, increased levels of PAI-1 have emerged as a masker for an increased thrombolic risk. This article represents a status report of mechansism of action, regulation of plasma levels, as well as the role of PAI-1 in arterial and venous thromboembolic disease.     

冠心病患者血清脂蛋白(a)与纤溶功能的变化及其相关性

目的:观察冠心病(CHD)患者血清脂蛋白a[Lp(a)]、血浆组织型纤溶酶原激活剂(tPA)与纤溶酶原激活剂抑制物-1(PAI-1)活性的变化特点,并探讨它们之间的关系。方法:对124例CHD患者和26例正常人采用双抗体ELISA法测定Lp(a)浓度,发色底物法测定tPA、PAI-1活性。结果:CHD患者中,急性心肌梗死(AMI)和不稳定性心绞痛(UAP)组患者Lp(a),浓度和PAI-1活性均非常显著高于对照组(P<0.01):tPA活性显著低于对照组(P<0.01);陈旧性心肌梗死(OMI)和稳定性心绞痛(SAP)组患者Lp(a)浓度和PAI-1活性均亦高于对照组(P<0.05);tPA活性亦低于对照组(P<0.05)。124例CHD患者相关分析显示:Lp(a)与PAI-1活性呈显著正相关,与tPA活性呈显著负相关(P均<0.001)。结论:冠心病患者Lp(a)显著升高,且与tPA、PAI-1活性有密切相关关系。     

Hyperinsulinemia predicts low tissue plasminogen activator activity in a healthy population: The Northern Sweden MONICA study

Fibrinogen levels predict atherothrombotic disease, and impaired fibrinolysis has been proposed as a risk factor for myocardial infarction. Fibrinolysis is mainly dependent on the activity of tissue plasminogen activator (tPA) and its inhibitor plasminogen activator inhibitor type-1 (PAI-1). Oral glucose tolerance tests were performed in 318 randomly selected healthy men and 324 women aged 25 to 64 years. tPA activity was strongly predicted by fasting insulin in both univariate analysis (r = −.37 and −.34 in men and women, respectively) and multivariate analysis with age, anthropometric measurements, lipids, and blood pressure included. Fasting insulin was the strongest predictor of PAI-1 activity (r = .49 and .51). In women, the influence of fasting insulin level on tPA and PAI-1 activity was consistently stronger after than before menopause, and a threshold effect was seen with distinctly lower fibrinolytic activity in the highest quartile of insulin (>7.0 mU/L). In men, the relation between insulin and fibrinolytic variables was linear. Fibrinogen levels were not related to insulin or glucose levels after adjustment for age and other risk factors in a multiple regression. Subjects with previously unknown diabetes or impaired glucose tolerance tended to have elevated fibrinogen and PAI-1 activity and decreased tPA activity. Our data support previous findings of a strong correlation between insulin and PAI-1 activity in small highly selected groups, and extend them to randomly selected population samples. The strong inverse relation between endogenous insulin levels and tPA activity has not previously been demonstrated in a healthy population.     

Impaired fibrinolysis and insulin resistance in patients with hypertension

Plasma plasminogen activator inhibitor type 1 (PAI-1) and tissue plasminogen activator (tPA) antigens and activities were measured in 28 patients with hypertension and 12 normal controls. Steady state plasma glucose (SSPG) concentrations were also determined after an infusion of somatostatin, insulin and glucose. Patients with hypertension were further subdivided into two groups: insulin resistance (SSPG > 190 mg/dL, n = 14) and no insulin resistance (SSPG < 190 mg/dL, n = 14). As compared to normal controls, hypertensive patients, either with or without insulin resistance, had significant (P < .005) increases in PAI-1 activity (18.6 ± 1.3 ν 8.1 ± 0.8 IU/mL), PAI-1 antigen (31.1 ± 2.0 ν 12.7 ± 0.9 ng/mL) and tPA antigen (15.5 ± 0.9 ν 8.8 ± 0.9 ng/mL), and significant decrease in tPA activity (0.43 ± 0.05 ν 1.02 ± 0.16 IU/mL) than normotensive controls. Furthermore, hypertensive patients with insulin resistance had significantly higher PAI-1 activity (22.0 ± 2.2 ν 15.3 ± 0.8 IU/mL, P = .006) and tPA antigen (17.4 ± 1.2 ν 13.6 ± 1.3 ng/mL, P = .02) than did hypertensive patients without insulin resistance. However, PAI-1 antigen was insignificantly higher (34.1 ± 2.9 ν 28.1 ± 2.4 ng/mL, P = .06) and tPA activity insignificantly lower (0.42 ± 0.08 ν 0.43 ± 0.08 IU/mL, P = .45) in hypertensive patients with insulin resistance than in those without insulin resistance. In addition, PAI-1 activity and tPA antigen were significantly correlated with blood pressure, SSPG, triglyceride, HDL-cholesterol and integrated glucose response to an oral load of 75 g glucose. Thus, patients with hypertension have impaired fibrinolytic activity due to increased PAI-1 when compared to normotensive controls, and the magnitude of this fibrinolytic defect is greater in hypertensive patients who have insulin resistance. Insulin resistance with associated metabolic abnormalities may be one of the causes for impaired fibrinolysis in hypertension.     

Bradykinin stimulates the release of tissue plasminogen activator in human coronary circulation: effects of angiotensin-converting enzyme inhibitors

OBJECTIVES: The goal of this study was to determine: 1) whether bradykinin (BK) directly stimulates tissue plasminogen activator (tPA) secretion in human coronary circulation, and 2) whether angiotensin-converting enzyme (ACE) inhibition favorably alters the fibrinolytic balance regulated by BK. BACKGROUND: Bradykinin is a potent stimulator of tPA secretion in endothelial cells; however, the effect of BK on tPA release in the human coronary circulation has not been studied. METHODS: Fifty-six patients with atypical chest pain were randomly assigned to two groups: 25 patients were treated with the ACE inhibitor enalapril (ACE inhibitor group), and 31 were not treated with ACE inhibitors (non-ACE inhibitor group). Graded doses of BK (0.2, 0.6, 2.0 microg/min), acetylcholine (ACh) (30 microg/min) and papaverine (PA) (12 mg) were administered into the left coronary artery. Coronary blood flow (CBF) was evaluated by Doppler flow velocity measurement. Blood samples were taken from the aorta (Ao) and the coronary sinus (CS). RESULTS: Bradykinin induced similar increases in CBF in both groups. The net tPA release induced by BK was dose-dependently increased in both groups, and the extent of that increase in the ACE inhibitor group was greater than that in the non-ACE inhibitor group. Bradykinin did not alter plasminogen activator inhibitor-1 (PAI-1) levels in the Ao or CS in either group. Neither ACh nor PA altered tPA levels or PAI-1 levels in either group. CONCLUSIONS: Intracoronary infusion of BK stimulates tPA release without causing any change in PAI-1 levels in the human coronary circulation. In addition, this effect of BK is augmented by an ACE inhibitor.     

Circadian activity of the endogenous fibrinolytic system in stable coronary artery disease: effects of beta-adrenoreceptor blockers and angiotensin-converting enzyme inhibitors

Objectives. To examine circadian changes in the sympathovagal balance, the activity of the renin-angiotensin system and hemostatic variables in patients with stable coronary artery disease, and the effects of beta-adrenoceptor blockade and angiotensin-converting enzyme inhibition.

Background. Sympathovagal balance and key components of the fibrinolytic system show circadian variability. The effects of beta-adrenergic blocking agents and angiotensin-converting enzyme inhibitors on these autonomic and hemostatic rhythms are not well defined.

Methods. Twenty patients with coronary artery disease underwent 24-h Holter monitoring for heart rate variability and blood sampling (6 hourly for 24 hours) after three consecutive treatment phases, (firstly with placebo, then bisoprolol, and finally quinapril). The effects on sympathovagal balance, hemostatic variables and the renin-angiotensin system activity were measured.

Results. The fibrinolytic capacity showed marked circadian variation at the end of the placebo phase (p = 0.002), plasminogen activator inhibitor-1 (PAI-1) activity peaking at 06.00 am when tissue plasminogen activator (tPA) activity was at its nadir. Sympathovagal balance showed a sharp increase at approximately the same time but plasma renin activity did not rise until later in the day. Inspection of the 24-h profiles suggested that bisoprolol reduced sympathovagal balance and the morning peak of PAI-1 activity and antigen, with a small increase in tPA activity, although these changes were not significant. Quinapril produced a substantial rise in renin (p = 0.01) but did not significantly affect either PAI-1 or tPA. Sympathovagal balance was unaffected by quinapril.

Conclusions. In patients with stable coronary artery disease, angiotensin-converting enzyme inhibition with quinapril does not affect either sympathovagal balance or the endogenous fibrinolytic system. Our data suggest that the sympathoadrenal system may modify fibrinolytic activity, judged by the response to beta-adrenoreceptor blockade with bisoprolol.     

缓释异搏定和开搏通对高血压病纤溶活性的影响

采用发色底物法测定了50例Ⅰ、Ⅱ期高血压病(EH)患者组织型纤溶酶原激活剂(t-PA)及其抑制物(PAI-1)活性,并与25例正常人对照.其中21例EH患者接受缓释异搏定治疗,19例EH患者接受开搏通治疗,共12周.结果显示:EH患者t-PA活性下降(P<0.05),PAI-1活性升高(P<0.05).缓释异搏定和开搏通有效降压12周后,t-PA活性升高,PAI-1活性降低.提示EH患者纤溶活性下降,缓释异搏定和开搏通在有效降压的同时能改善高血压患者的纤溶活性.     

Independent relationship between microalbuminuria and plasminogen activator inhibitor-1 activity (PAI-1) activity in clinically healthy 58-year-old men.

The aim of this cross-sectional study was to investigate the relationship between low-grade albuminuria (microalbuminuria) and factors of the coagulation- and fibrinolysis systems in 104 clinically healthy 58-year-old men recruited from the general population. Urinary albumin excretion was significantly associated with body mass index, systolic and diastolic blood pressure, plasminogen activator inhibitor (PAI)-1 activity, tissue plasminogen activator (tPA) antigen, tPA activity (negatively) and protein S (P<0.05). There were no associations between urinary albumin excretion and antithrombin III, fibrinogen, protein C, thrombin/antithrombin factor or von Willebrand factor. In multiple regression analysis urinary albumin excretion was independently and significantly associated with PAI-1 activity and systolic blood pressure (P<0.05). In conclusion we report that urinary albumin excretion was independently and significantly associated with PAI-1 activity in clinically healthy 58-year-old men. This relationship may contribute to the previously reported increased cardiovascular morbidity in subjects with microalbuminuria.     

氯沙坦对高血压病患者尿白蛋白及纤溶活性的影响

目的　探讨尿白蛋白排泄率与纤溶活性的关系及氯沙坦对其影响。方法　选择 6 2例高血压病伴轻、中度肾功能损害 (肌酐清除率 <70mL/min ,但≥ 30mL/min)患者 ,经随机分为两组分别予氯沙坦 5 0～ 10 0mg/d或卡托普利75～ 15 0mg/d降压治疗 12周。同时选择 2 4例高血压病伴肾功能完全正常 (肌酐清除率≥ 80mL/min)患者作为对照组 ,降压治疗前后分别测定尿白蛋白排泄率 (UAE)、纤溶酶原激活剂活性 (tPA)、纤溶酶原激活抑制剂活性 (PAI)。结果　肾功能异常组UAE、PAI均升高 (P <0 0 1) ,tPA降低 (P <0 0 5 ) ;UAE与tPA ,PAI,PAI/tPA相关系数分别为 0 2 0 (P >0 1)、0 32 (P <0 0 5 )、0 34(P <0 0 1) ,UAE与纤溶活性降低正相关 ;降压治疗后两组均降低UAE、PAI(P <0 0 1) ,卡托普利组还升高tPA(P <0 0 5 )。结论　肾功能异常时纤溶活性降低 ,肾功能损害与纤溶降低有关 ,氯沙坦及卡托普利改善肾功能 ,也改善纤溶活性。