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.     

Comparison of effects of enalapril and nitrendipine on cardiac sympathetic nervous system in essential hypertension

Objectives. The purpose of this study was to assess the effects of enalapril and nitrendipine on the cardiac sympathetic nervous system.Background. Angiotensin-converting enzyme inhibitors and long-acting calcium channel blockers have been widely used in the treatment of cardiovascular diseases, in some of which sympathetic overactivity plays a major role in the pathophysiology and prognosis. However, little information is available on the effects of these drugs on the cardiac sympathetic nervous system.Methods. ¹²³I-metaiodobenzylguanidine (MIBG) cardiac imaging was performed before and 3 months after drug administration in 46 patients with mild essential hypertension. Twenty-two patients were treated with 5 to 10 mg of enalapril once a day, and the other 24 with 5 to 10 mg of nitrendipine once a day. For comparison, 20 normotensive subjects were also studied.Results. There were no significant differences between the basal characteristics in the 2 hypertensive groups. In both hypertensive groups, both systolic and diastolic blood pressures were significantly reduced to similar levels after the 3-month drug treatment. Before the drug treatment, the 2 hypertensive groups had a significantly higher washout rate and lower MIBG uptake than the normotensive subjects. The heart-to-mediastinum ratio significantly increased (p < 0.0001), with decreased (p < 0.002) washout rate after drug treatment in the enalapril group, but with no significant changes in the nitrendipine group.Conclusion. Enalapril could suppress cardiac sympathetic activity and nitrendipine had no effect on it. The knowledge of antihypertensive drugs on the cardiac sympathetic nervous system appears to be helpful in selecting appropriate treatment in cardiovascular diseases.     

厄贝沙坦与非洛地平对原发性高血压纤溶系统影响的比较

目的 :通过比较厄贝沙坦和非洛地平对原发性高血压 (EH)患者纤溶系统的影响 ,探讨在改善EH纤溶障碍方面厄贝沙坦是否优于非洛地平。方法 :5 3例 1、2级EH患者随机分为厄贝沙坦组 2 8例 (厄贝沙坦15 0mg/d)和非洛地平组 2 5例 (非洛地平 5mg/d) ,共服药物 2周 ,观察治疗前后血压、血浆组织型纤溶酶原激活物 (tPA)及其抑制物 (PAI 1)含量、D 二聚体 (D D)和血管性血友病因子 (vWF)水平的变化。结果 :两组患者的基本资料差异无显著性意义 (P >0 .0 5 ) ,两组患者治疗后血压均显著性下降 (P <0 .0 1) ,但两组之间治疗前后血压相比差异无显著性意义 (P >0 .0 5 )。治疗后两组PAI 1、vWF和D D水平均显著下降 (P <0 .0 5 ) ,tPA和tPA/PAI 1比值明显升高 (P <0 .0 5 )。两组之间治疗前的tPA、PAI 1、D D和vWF含量差异均无显著意义 ,治疗后的D D和vWF水平差异也无显著性意义 ,但PAI 1含量在厄贝沙坦组减少更明显 (P <0 .0 5 ) ,tPA和tPA/PAI 1比值在厄贝沙坦组增加更显著 (P <0 .0 5 )。结论 :厄贝沙坦和非洛地平均能有效改善EH的纤溶障碍 ,但厄贝沙坦优于非洛地平     

Effects of candesartan and lisinopril on the fibrinolytic system in hypertensive patients

The effects of the angiotensin II receptor blocker candesartan and the angiotensin-converting enzyme inhibitor lisinopril on the fibrinolytic system were investigated in a double-blinded, prospective, randomized study. Seventy-seven hypertensive patients taking candesartan (n=41) and lisinopril (n=36) with a systolic blood pressure >130 mm Hg and/or a diastolic blood pressure >80 mm Hg obtained by 24-hour ambulatory blood pressure measurement were included in the study. Blood pressure, plasminogen activator inhibitor 1 (PAI-1), tissue plasminogen activator (tPA), and the molar ratio of PAI-1/tPA were determined before treatment and 6 weeks later. Blood pressure decreased in both groups (candesartan, 155/85 mm Hg to 140/84 mm Hg; P<.05; lisinopril, 152/85 mm Hg to 138/83 mm Hg; P<.05). The fibrinolytic balance was significantly different between treatment groups (molar ratio of PAI-1/tPA: candesartan, 3.66 [2.2;] lisinopril, 5.44 [2.6;] P<.05). In contrast to lisinopril, the balance between coagulation and fibrinolytic activity shifted toward fibrinolysis during candesartan treatment.     

氯沙坦和依那普利对心肌梗死后纤溶-凝血功能的影响

目的　探讨氯沙坦和依那普利对急性心肌梗死 (AMI)患者纤溶 凝血功能的影响。方法　将 41例AMI患者随机分为氯沙坦组、依那普利组和对照组 ,以发色底物法和ELISA法测定三组患者入院即刻、发病 2周、2个月的血浆PAI 1活性、纤溶酶原激活物 (tPA)抗原水平和血管血友病病因子(vWF)含量。结果　与对照组相比 ,氯沙坦组 2周和 2个月时的PAI 1活性分别减低 2 2 % (P <0 0 1)和 18% (P <0 0 5 ) ,tPA抗原水平分别减低 32 % (P <0 0 1)和 2 5 % (P <0 0 5 ) ;依那普利组相应分别减低 2 8% (P <0 0 1)和 2 1% (P <0 0 5 ) ,tPA抗原水平分别减低 38% (P <0 0 1)和 2 9% (P <0 0 5 ) ;两个治疗组之间差异无显著性。两种药物对vWF含量均无影响。结论　氯沙坦和依那普利可改善心肌梗死后的纤溶功能 ,长期应用这两种药物可能会降低心肌梗死后发生急性心脏事件的危险。     

The impact of angiotensin II receptor blockade and the DASH diet on markers of endogenous fibrinolysis

Hypertension is associated with impaired fibrinolysis. Both angiotensin receptor blockers (ARB) and the DASH (Dietary Approaches to Stop Hypertension) diet effectively lower blood pressure in hypertensive patients. Some evidence suggests that treatment with ARBs could increase fibrinolysis, however, data is conflicting. The impact of the DASH diet on fibrinolytic parameters is not known. Fifty-five hypertensive participants (35 African-American, 20 white) were randomly assigned to receive 8 weeks of either a control diet or the DASH diet. The diets did not differ in sodium content (approximately 3 g/day). Within each diet, individuals were randomly assigned to receive losartan or placebo for 4 weeks in double-blind, cross-over fashion. Tissue plasminogen activator (t-PA) antigen, t-PA activity, plasminogen activator inhibitor-1 (PAI-1) activity and plasma renin activity (PRA) were measured at the end of a 2-week run-in period on the control diet and after each treatment period. The DASH diet did not affect markers of fibrinolysis. Losartan significantly lowered t-PA antigen levels (-1.8 ng/mL, P = 0.045), but had no effect on t-PA or PAI-1 activities. This effect was more pronounced in whites (-4.1 ng/mL (P = 0.003)) compared with African-Americans (-0.3 ng/mL (P = 0.7), P-interaction = 0.03). Results were not materially affected by adjustment for basline values or changes in blood pressure. This study demonstrates that losartan reduces t-PA antigen levels in white, but not African-American hypertensive individuals. In contrast, the DASH diet had no significant effect on markers of fibrinolysis in whites or African-Americans.     

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。     

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.     

Antihypertensive Drug Treatment and Fibrinolytic Function

Thromboembolic complications such as ischemic stroke and myocardial infarction are significantly more frequent in patients with arterial hypertension. From the available intervention studies, it appears that pharmacologic treatment of hypertension—at least with diuretics and β-blockers—may more effectively protect against cerebrovascular as compared to coronary thromboembolic events. Whether other antihypertensive substances provide a more effective protection with respect to cardiac morbidity and mortality is the subject of numerous studies presently underway. These studies will help to answer the question of whether the extent of protection from coronary events during antihypertensive treatment depends on factors beyond blood pressure control. The fibrinolytic system is crucially involved in the pathogenesis of thromboembolic events. One determinant of this system is the balance between plasminogen activators (tissue-type plasminogen activator [t-PA]) and inhibitors (plasminogen activator inhibitor 1 [PAI-1]). Experimental and clinical evidence suggests that at least some of the drugs used in the treatment of hypertension may alter the activity of the fibrinolytic system. Scarce and controversial data with respect to such an interaction exist with respect to diuretics, β-blockers, and calcium antagonists. In addition, experimental evidence demonstrates that PAI-1 is stimulated by angiotensin II (A II), whereas t-PA is activated by bradykinin. Thus, antihypertensive drugs acting within the renin angiotensin system should exert effects also within the fibrinolytic system. However, results from clinical studies with angiotensin converting enzyme (ACE) inhibitors and A II receptor antagonists do not unequivocally support such a concept. The discrepancy in the results may, at least in part, be explained by studies performed in healthy volunteer subjects showing that ACE inhibition profoundly affected fibrinolysis only during stimulation of the renin angiotensin system by NaCL restriction.     

高血压病人纤维蛋白原水平及纤溶系统功能研究

为了解高血压病人的血栓形成倾向,我们随机选取了４１例高血压病人及３４例正常血压者,分别观察了他们的纤维蛋白原及血浆组织型纤溶酶原激活物（ｔＰＡ）抗原及纤溶酶原激活物抑制物－１（ＰＡＩ－１）的含量。结果表明,高血压病人血浆纤维蛋白原水平无明显变化,但ｔＰＡ抗原含量减少,ＰＡＩ－１的水平增加。提示高血压病人存在内源性纤溶功能受损     

Antihypertensive drugs and fibrinolytic function

Impaired fibrinolytic function, characterized by increased plasminogen activator inhibitor type 1 (PAI-1) levels and decreased tissue plasminogen activator (t-PA) activity, has been found in patients with hypertension and may account in part for the increased risk of atherosclerosis and its clinical complications in these patients. Failure to correct this prothrombotic state may be one of the possible reasons for the disappointing effect of antihypertensive treatment on the incidence of coronary events. In this regard, data from the literature indicate that different antihypertensive drugs may vary in their influence on fibrinolysis. Scarce and conflicting data exist regarding the effects of diuretics and beta-blockers on the fibrinolytic system. Angiotensin-converting enzyme (ACE) inhibitors (ACE-I) have generally been shown to improve the fibrinolytic balance by reducing plasma PAI-1 levels, calcium channel blockers (CCB) have been reported to increase t-PA activity, and angiotensin receptor blockers (ARB) seem to be neutral in their effect. Interesting data have been reported about the positive impact on fibrinolysis of combining an ACE-I with a CCB, which resulted in a decrease of PAI-1 caused by ACE inhibition, and an increase in t-PA resulting from calcium channel blockade. The positive effect of ACE-I on the fibrinolytic system has been related to: 1) inhibition of angiotensin II, which stimulates PAI-1 expression; 2) inhibition of degradation of bradykinin, a potent stimulus for tPA production; and 3) improvement of insulin sensitivity. The mechanisms underlying the CCB effect on t-PA are less clear, but a direct action of CCB on vascular endothelium has been reported to play a major role. The greater improvement in the fibrinolytic balance because of the combined action of ACE inhibition and Ca antagonism represents a further indication to the use of combinations of ACE-I and CCB in the treatment of hypertension.     

Effect of antihypertensive therapy using enalapril or losartan on haemostatic markers in essential hypertension: a pilot prospective randomised double-blind parallel group trial

To test the hypothesis that the hypercoagulable state in hypertension is significantly altered by anti-hypertensive therapy, we conducted a pilot prospective randomised double-blind trial of 40 untreated hypertensive patients (30 males, mean age 59 years) who were treated with either enalapril (10-20 mg per day) or losartan (50-100 mg per day) for 8 weeks. Thrombogenicity was assessed by measurement of plasma fibrinogen, soluble P-selectin (an index of platelet activation), plasminogen activator inhibitor 1 (PAI-1, an index of fibrinolysis) and von Willebrand factor (an index of endothelial dysfunction). Baseline von Willebrand factor alone was significantly higher in untreated hypertensive patients compared to controls (P<0.001). Following 8 weeks treatment with enalapril (mean dose 17 mg/day) or losartan (mean dose 77 mg/day), there was a significant reduction in mean blood pressure from 169+/-11/94+/-8 mmHg (baseline) to 147+/-14/84+/-7 mmHg (post-treatment) (P<0.001). However, there were no statistically significant changes in the levels of haemostatic markers (von Willebrand factor, fibrinogen, s-Psel and PAI-1). Our pilot study confirms previous observations of endothelial dysfunction in hypertensives. However, plasma fibrinogen and indices of platelet activation, fibrinolysis or endothelial dysfunction were not significantly affected by antihypertensive treatment with enalapril or losartan, despite satisfactory blood pressure control.     

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.     

疏血通注射液对心房颤动患者血栓前状态的影响

目的研究疏血通注射液对心房颤动患者血栓前状态的改善作用。方法将63例心房颤动患者随机分为疏血通组和对照组,疏血通组应用疏血通注射液治疗14d,对照组除不使用疏血通,其他用药与疏血通组相同。治疗前和治疗2周后测量两组血浆纤溶酶原激活物(tPA)及其抑制物(PAI-1)活性,D-二聚体(D-D)和血管性假血友病因子(vWF)水平。结果疏血通组和对照组在治疗前血浆tPA、PAI-1活性、D-D和vWF水平无统计学意义(P>0.05)。疏血通组治疗后血浆tPA活性显著性增高(P<0.05),血浆PAI-1活性、D-D和vWF水平均显著性下降(P<0.05),而对照组无显著性改变(P>0.05)。组间比较发现,疏血通组治疗后血浆PAI-1活性、D-D和vWF水平比对照组更低(P<0.05),而血浆tPA活性无显著增高(P>0.05)。结论短期疏血通静脉输注可以明显改善心房颤动患者的血栓前状态,这可能降低心房颤动患者的血栓栓塞危险。     

Effects of lisinopril, irbesartan, and amlodipine on the thrombogenic variables in the early and late stages of the treatment in hypertensive patients

Regulation of the fibrinolytic balance between plasminogen activators and inhibitors is modulated by the renin-angiotensin system (RAS). Impaired fibrinolytic function, characterized by increased plasminogen activator inhibitor type 1 (PAI-1) levels and decreased tissue plasminogen activator (t-PA) activity, has been found in patients with hypertension and may account in part for the increased risk of atherosclerosis and its clinical complications in these patients. In this regard, data from the literature indicate that different antihypertensive drugs may vary in their influence on fibrinolysis. Angiotensin-converting enzyme (ACE) inhibitors (ACE-I) have generally been shown to improve the fibrinolytic balance by reducing plasma PAI-1 levels. Calcium-channel blockers (CCB) have been reported to increase t-PA activity, and angiotensin receptor blockers (ARB) seem to be neutral in their effect. In the light of these data, this study aimed to compare the effects of ACE-I, ARB, and CCB on the fibrinolytic system in the early and late stages of the treatment in hypertensive patients. These data that the beneficial effect of RAS inhibition on fibrinolysis related to decrease in Ang II during early period of treatment. Amlodipine may also improve thrombogenic risk related to lowering the effect on increased platelet activation reflected by p-selectin. The greater improvement in the early and late stages of the fibrinolytic balance because of the combined action of RAS inhibition and Ca antagonism represents a further indication to the use of combinations of RAS inhibition (ACE-I or ARB) and CCB in the treatment of hypertension.     

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。     

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.     

Effects of amlodipine and cilnidipine on cardiac sympathetic nervous system and neurohormonal status in essential hypertension.

N-Type calcium channel antagonists may suppress sympathetic activity. The purpose of this study was to assess the effects of amlodipine and cilnidipine on the cardiac sympathetic nervous system and the neurohormonal status of essential hypertension. 123I-metaiodobenzylguanidine (MIBG) cardiac imaging was performed and blood samples were taken to determine plasma renin activity and plasma norepinephrine concentration before and 3 months after drug administration in 47 patients with mild essential hypertension. Twenty-four of the patients were treated with 5 to 10 mg/d of amlodipine; the other 23 were treated with 10 to 20 mg/d of cilnidipine. For comparison, 12 normotensive subjects were also studied. No significant differences were found in the basal characteristics between the 2 hypertensive groups. In both hypertensive groups, both the systolic and diastolic blood pressures were significantly reduced to similar levels 3 months after drug treatment. Before the drug treatment, the 2 hypertensive groups had a significantly higher washout rate and lower heart-to-mediastinum (H/M) ratio compared with the normotensive subjects. The H/M ratio significantly increased (P<0.05) in combination with a decreased washout rate (P<0.02) after drug treatment in the cilnidipine group. In the amlodipine group, a significant decrease in washout rate (P<0. 04) was noted, without an increase in the H/M ratio. However, no significant changes were found in plasma renin activity and plasma norepinephrine concentration in either group. Thus, in patients with essential hypertension, cilnidipine suppressed cardiac sympathetic overactivity and amlodipine had a little suppressive effect. Cilnidipine may provide a new strategy for treatment of cardiovascular diseases with sympathetic overactivity.     

Glycaemic Control,Smoking Habits and Diabetes Duration Affect the Extrinsic Fibrinolytic System in Type I Diabetic Patients but Microangiopathy Does Not

ABSTRACT The fibrinolytic system was studied in 43 type I diabetic patients with long duration of the disease, with or without evidence of microangiopathy, and in 26 control subjects. There were positive and independent correlations between tissue plasminogen activator (tPA) activity after venous occlusion and HbA_lc, and between triglycerides and plasminogen activator inhibitor (PAI-1) and tPA antigen concentrations before and after venous occlusion. The tPA activities both at rest and after venous occlusion were higher in the patients. There were no differences with regard to sex, hypertension or nephropathy for the levels of fibrinolytic variables in these patients. Subjects with retinopathy did not differ from those without retinopathy. Diabetes duration showed a significant negative association with tPA activity in multivariate regression analysis. Tobacco-smoking diabetics, as compared to non-smoking, had an increased tPA antigen release at venous occlusion, but also higher PAI-1 levels and reduced specific activity of the tPA protein. When assessed with the new specific assays now available, the fibrinolytic parameters appear to be specific indicators of endothelial dysfunction related to smoking and to degree of glycaemic control in type I diabetic subjects.     

持续气道正压通气对OSAHS患者血管内皮细胞及纤溶系统的影响

为探讨经鼻持续气道正压通气（nCPAP)治疗前后阻塞性睡眠呼吸暂停低通气综合征（OSAHS）患者血管内皮细胞及纤溶系统的变化及临床意义，选择年龄，性别，体重指数（BMI）无明显差异的OSAHS患者38例和健康者对照组32例，用多导睡眠呼吸监测仪进行监测，以凝固法测定纤维蛋白原（Fg），发色底物法测组织纤溶酶原激活物活性（tPA：A）、纤溶酶原激活物抑制物－1活性（PAI－1：A），酶联免疫法测vonWillebrand因子（vWF)、组织纤溶酶原激活物抗原（tPA:Ag）、纤溶酶原含量（PLg:Ag)和纤溶酶原激活物抑制物－1含量（PAI－1：Ag）。结果OSAHS组与对照组比较，vWF,Fg,tPA:Ag、PAI－1：A明显升高（P分别＜0．01，0．001，0．001，0．01），PLg:Ag、tPA:A、tPA:Ag、最低血氧饱和度（SaO2low)明显降低（P分别＜0．01，0．001，0．001，0．01).nCPAP治疗后与治疗前比较，vWF,Fg,PAI-1:Ag,PAI-1:A明显降低（P分别＜0．05，0．01，0．01，0．01），PLg:Ag,tPA:A,tPA:Ag，最低SaO2明显升高（P分别＜0．05，0．001，0．001，0．01）。提示OSAHS患者血管内皮细胞损伤，凝血功能增强，纤溶系统功能减弱;nCPAP治疗能部分纠正各指标的异常。