Analysis of the mechanism of action of bradykinin on human basilar artery in vitro

Summary Bradykinin (BK) initially produced concentration-related relaxations of human basilar artery in vitro. Concentration-effect curves constructed at 2 h intervals to BK over an 8 h period were reproducible. The rank order of potency of three kinins on the human basilar artery was found to be BK > methionyl-lysyl-BK > des-Arg⁹-BK. The B₂-receptor antagonist Thi^5,8 d-Phe⁷-BK but not the B₁-receptor antagonist des-Arg⁹-Leu⁸-BK selectively blocked BK-induced relaxations of the human basilar artery.The relaxant effects of bradykinin and acetylcholine but not papaverine were attenuated after removal of the endothelium or treating the tissues with BW755C. Indomethacin was without effect. Concentration-effect curves to angiotensin I were markedly attenuated by captopril at a concentration which had no effect on BK, angiotensin II or 5-hydroxytryptamine responses. It is concluded that BK induced relaxations of the human basilar artery are mediated via activation of a B₂ receptor and the response is dependent upon the release of a factor present in the endothelium. Angiotensin converting enzyme is present in the human basilar artery and is important for the conversion of angiotensin I to angiotensin II but apparently not for the degradation of BK. It is likely that other kininases are present and active in the tissue. Send offprint requests to E. T. Whalley at the above address     

Cardiovascular risk factors in people with different genotypes in the insertion/deletion (I/D) polymorphism at the locus for angiotensin I-converting enzyme (ACE)

The deletion (D) allele of an insertion/deletion (I/D) polymorphism at the locus for angiotensin I-converting enzyme (ACE) has been reported to be an independent risk factor for myocardial infarction (MI), particularly in people lacking traditional risk factors. Furthermore, a borderline association between Lp(a) lipoprotein level and the I/D polymorphism at the ACE locus was reported in one study. We have searched for possible "level gene" or "variability gene" effects of ACE genes on Lp(a) lipoprotein, total cholesterol (TC), high density lipoprotein (HDL) cholesterol (HDLC), low density lipoprotein (LDL) cholesterol (LDLC), triglycerides (TG), apolipoprotein B (apoB), apolipoprotein A-I (apoA-I), and body mass index (BMI). None of these variables differed significantly between genotypes in the I/D polymorphism in any of three population samples. A single population sample created by combining the three series, exhibited an insignificant trend towards individuals carrying the D-allele having a higher level of Lp(a) lipoprotein than those lacking it, and DD homozygotes had a significantly higher Lp(a) lipoprotein level than the combined group of ID/II individuals (p = 0.03). These results may indicate that the D-allele of the I/D polymorphism at the ACE locus could influence the level of Lp(a) lipoprotein.     

糖尿病肾病防治新观点--美国第84届内分泌协会年会专题小结

糖尿病肾病是导致糖尿病死亡及终末期肾病透析的主要原因之一。在美国第84届内分泌协会年会上报告了一些糖尿病肾病治疗新观点。内容包括：HOPE研究结果；血管紧张素转换酶抑制剂(ACEI)是糖尿病患者心血管甚至是肾功能不全的保护药；ACEI可能能够预防糖尿病；血管紧张素1(AT1)受体阻滞剂(ARB)肾保护作用的证据；糖尿病中血压控制的重要性；ARB改善这些患者充血性心力衰竭及使用ACEI和ARB的临床建议等。本文对此作一综述。     

缺氧与复氧对培养的肺动脉内皮细胞功能的影响

缺氧与复氧均可引起肺血管收缩和损伤，本研究观察肺血管内皮细胞活力和血管紧张素转换酶（ＡＣＥ）释放在其中的作用。培养的新生小牛肺动脉内皮细胞（ＰＡＥＣ）在缺氧条件下（０％Ｏ２－９５％Ｎ２）培养６～２４ｈ，其上清液ＡＣＥ活性无显著变化，而细胞活力于缺氧１２～２４ｈ显著增加（与常氧组相比增加２０％～３３％，Ｐ＜０．０５）。ＰＡＥＣ在缺氧条件下培养２４ｈ，复氧培养３～６ｈ后其上清液ＡＣＥ活性显著增加（与常氧组和缺氧组相比Ｐ＜０．０１），于１２ｈ恢复至复氧前的水平。细胞活力的变化与ＡＣＥ的变化类似，复氧３～６ｈ显著高于常氧水平（Ｐ＜０．０１与常氧组相比），１２ｈ恢复至正常。上述结果表明ＰＡＥＣ的ＡＣＥ和细胞活力的变化可能对肺动脉壁本身ＲＡＳ功能的调节及缺氧性肺血管收缩的发生起一定作用。     

检测血管紧张素转化酶在AFP阴性肝癌诊断中的价值

目的　探讨肝癌患者血清血管紧张素转化酶 (ACE)活性变化对AFP阴性肝癌 (HCC)患者诊断及鉴别诊断的价值。方法　选择经组织学 (肝穿刺 )或影像学确诊的 38例HCC患者 ,2 1例慢性肝炎患者 ,12例肝硬化患者及 2 0例正常健康对照者 ,检测血清AFP含量和ACE活性。结果　与其他良性肝病相比HCC患者血清ACE活性 ( 19.51± 4 .4 6)显著低于慢性肝炎 ( 38.35± 6.34 ,P <0 .0 1)及肝硬化患者 ( 4 7.77± 10 .59,P <0 .0 1) ,并且也低于正常人 ( 30 .0 0± 2 .92 ,P <0 .0 5)。 2 3例AFP阳性 (≥2 0 0mg/L)HCC患者中 ,其ACE活性为 ( 19.15± 4 .2 6) ,与AFP阴性患者比较差异无显著性 (P >0 .0 5)。结论　检测血清ACE活性有助于肝癌 ,尤其是合并肝硬化或AFP阴性的患者的诊断。ACE和AFP联合检测有助于提高肝癌的检出率     

ACEI对血压正常的早期糖尿病肾病治疗作用的Meta分析

目的：对血管紧张素转换酶抑制剂（ＡＣＥＩ）能否延缓血压正常的早期糖尿病肾病（ｄｉａｂｅｔｉｃ ｎｅｐｈｒｏｐａｔｈｙ,ＤＮ）患者的病情进展进行系统评价。方法：检索ＭＥＤＬＩＮＥ及中国生物医学文献数据库中收录的１９９０年１月至１９９９年４月间,有关ＡＣＥＩ对伴微量白蛋白尿的早期ＤＮ治疗作用的随机对照临床试验方面的文献。按照入选标准,最终有１０项随机对照临床试验纳入本研究。用ＲｅｖＭａｎ３．１软件对１     

POLYMORPHISM OF ANGIOTENSIN-CONVERTING ENZYME GENE AND GENETIC SUSCEPTIBILITY TO ASTHMA WITH FAMILIAL AGGREGATION

Objective. Angiotensin-converting enzyme (ACE) plays a key role in the metabolism of angiotensin Ⅱ (AT Ⅱ) and inactivation of bradykinins and tachykinins, which are potent bronchialconstrictors and mediators of inflammation asthma, and ACE is heavily expressed in the lungs. An insertion-deletion (D/I) polymorphism of ACE gene has been shown to be associated with levels of ACE. We investigate whether the polymorphism of ACE gene is associated with asthma and bronchial responsiveness.Methods. A case-control study was carried out in 50 asthmatics, 7 families with at least 2 asthmatic individuals, and 50 healthy subjects. The insertion/deletion (I/D) polymorphism of ACE gene was amplified by polymerase chain reaction (PCR). Methacholine brocho-provocation and pulmonary function tests were performed in all asthmatics. Results. There was an higher gene frequency of DD genotype of ACE gene in asthmatic subjects and families individuals compared with healthy subjects (46%, 53% vs 16%, P＜0.05; odd ratio 4.98). Anhigher prevalence of DD genotype of ACE was in patients with bronchial hyperresposiveness (BHR) (67%vs 33%, P＜0.05; odd ratio 3.8). Accordingly, the mean values of FEV1% and FEV1/FVC were higher in asthmatics carrying non-DD alleles than patients with DD genotype (73.78% vs 56.56%, P＜0.05; 79.19% vs 69.29%, P＜0.05, respectively).Conclusion. These results suggested that DD allele of ACE genotype was significantly involved in genetic susceptibility to asthma. DD genotype of ACE might be a risk factor for the degree of airway obstruction, it could also be implicated in pathogenesis of bronchial hyperresponsiveness.     

Angiotensin converting enzyme inhibitor-induced angioedema: a report of two cases

Angioedema is a rare but potentially fatal side effect of angiotensin converting enzyme (ACE) inhibitors. We report for the first time, two children with systemic lupus erythematosus who developed acute angioedema after the long-term use of enalapril. Prompt recognition and appropriate management of ACE-induced angioedema prevented life-threatening complications. This report highlights the potential risks of angioedema associated with the use of ACE inhibitors in children. Patients should be advised to seek medical treatment immediately if they experience swelling of the face, neck, or tongue, and especially if they have trouble breathing, speaking, or swallowing. Received: 12 March 1999 / Revised: 8 June 1999 / Accepted: 8 June 1999     

血管紧张素转化酶基因多态性与终未期肾衰

目的阐明血管紧张素转化酶（ACE）基因多态性及循环中ACE水平不同在肾脏疾病进展中的意义。方法对50名终末期肾功能衰竭（ESRF）患者和60名正常人ACE基因多态性进行分析。结果ACE基因在ESRF组和正常人组杂合子型（DI）和缺失型（DD）明显高于正常人,而插入型（Ⅱ）的发生率ESRF明显低于正常人。结论ACE基因多态性与肾衰的发展及肾小球硬化的发生有一定联系,ACE基因多态性的分析,可望成为判断肾脏疾病患者预后的一个新的筛查指标。