长效钙拮抗剂与转换酶抑制剂单独和联合使用在降压和副作用方面的比较

目的比较长效钙拮抗剂与血管紧张素转换酶抑制剂(ACEI)单独和联合使用在降压和副作用方面的差异.方法对1995年1月至1999年12月间我科单独和联合使用长效二氢吡啶类钙拮抗剂与ACEI降压药治疗的645例高血压病患者进行分析.结果两片钙拮抗剂(n=154)、两片ACEI(n=219)和联合用药(n=272,钙拮抗剂和ACEI)三组治疗后血压均明显降低,但联合用药组在降收缩压方面最明显,而钙拮抗剂组在降舒张压方面最明显.在咳嗽方面,ACEI组发生率最高(21%),联合用药组次之(7%).在浮肿方面,钙拮抗剂组发生率最高(13%),联合用药组次之(6%).结论长效二氢吡啶类钙拮抗剂与羧基类ACEI联合用药不仅可增加降压效果,而且可减少咳嗽和水肿副作用.     

卡托普利:从多肽到小分子降血压药物的研发历程

卡托普利(Captopril)是第一个上市的血管紧张素转化酶抑制剂(angiotensin-converting enzyme inhibitors,ACEI)。主要用于防治高肾素型高血压等各类高血压,其研发源于巴西蛇毒中的一种缓激肽。本文综述了如何从天然多肽化合物到苗头化合物的发现,再到先导化合物的确定,最后到卡托普利上市的研发历程,期望对相关研究提供有价值的参考。     

五步蛇毒中血管紧张素转换酶抑制剂的研究

采用离子交换和凝胶过滤等方法，从中国五步蛇毒中分离提纯出一种血管紧张素转换酶抑制剂（ＡＣＥＩ），名为ＡＩ９３，该抑制剂经豚鼠回肠测定能加强舒缓激肽（Ｂｒａｄｙｋｉｎｉｎ，ＢＫ）的效应，再经高压纸电泳，ＨＰＬＣ和氨基酸组分分析鉴定为１３肽，不含脯氨酸，分子量约为１．４２ＫＤ，ＰＩ约为４．０，得率约是原毒的３．４‰，ＡＣＥ抑制活力测定ＩＣ５０浓度为１１．０μｍｏｌ／Ｌ，属竞争性抑制类型，Ｋｉ＝５．８μ     

Randomized prospective study of effects of benazepril in renal transplantation: an analysis of safety and efficacy

Background. Prolonging the survival of transplanted kidneys is one of major tasks of modern nephrology. Angiotensin-converting enzyme inhibitors (ACEIs) compose a class of antihypertensive agents that has established efficacy in the treatment of hypertension and in slowing the progression of diabetic nephropathy and chronic glomerulonephritis. ACEIs are not widely accepted as a standard medication in the treatment of hypertension in renal transplant recipients because of the potential risk for decreased renal blood flow and glomerular filtration rate associated with a single kidney and concomitant cyclosporin use. Methods. We undertook a prospective randomized study of ACEI (benazepril) treatment in 76 posttransplant patients to determine the safety, efficacy, and side-effect profile of benazepril. Forty-one patients were assigned to the benazepril group and 35 patients were assigned to the control group. Results. The mean arterial blood pressure at a 12-month follow-up was lower than that at the time of initiation of benazepril or control therapy, with a decrease from 101 ± 10 mmHg to 94 ± 7 mmHg (P < 0.05) in the benazepril group and from 102 ± 12 mmHg to 94 ± 10 mmHg in the control group after 12 months of treatment. The serum creatinine concentrations did not change throughout the follow-up period. Conclusions. Benazepril was demonstrated to be an effective antihypertensive without any unfavorable effects on graft function. A significant antiproteinuric effect of benazepril was observed in patients with overt proteinuria. Further follow-up of this patient population will contribute to the establishment of the long-term renoprotective effect of benazepril in renal allograft recipients. Received: June 12, 2002 / Accepted: August 5, 2002 Correspondence to:T. Moriyama     

依那普利致咳嗽1例

１病例患者，男，５８岁，回族。入院前间歇性头晕、头痛已５年，头痛以双颞部为著，无明显眩晕、耳鸣、恶心、呕吐，视力正常，血压为１４０／１００mmHg，血糖、血脂正常，曾被诊断为“高血压病”。长期服用北京降压０号，血压控制在１３０～１４０／８０～９５mmHg之间。入住我院前１月，上述症状加重，以“高血压病”收住。１．１体格检查T３６．２℃，R１８次／分，P８４次／分，BP１４０／１０５mmHg。神志清，瞳孔等大等圆，对光反射灵敏，颈软。双肺叩清。未闻及异常呼吸音，心界不大，心率８４次／分，律齐，心前区可闻及Ⅲ／…     

细胞内游离钙在ACEI逆转SHR血管重构中的作用

目的：探讨细胞内游离钙在血管紧张素转换酶抑制剂(ACEI)逆转自发性高血压大鼠(SHR)血管重构中的作用。方法：采用SHR、正常血压大鼠(WKY)配对，服药前后对比及离体血管、淋巴细胞药物处理研究。结果：①SHR与WKY比较有以下血管重构现象：血管内膜有WBC粘附和侵袭，中层血管平滑肌细胞(VSMC)排列紊乱、纤维成分增多；血管内皮细胞及VSMC线粒体增多，体密度增加、肿胀，肌浆网扩张，比表面减少。②SHR外用淋巴细胞[Ca^2 ]i，主动脉平滑肌^45Ca静息内流，血浆血管紧张素Ⅱ浓度[ATⅡ]均较WKY显增加；③ACEI治疗后SHR血管重构现象得到逆转，血浆[ATⅡ]、淋巴细胞[Ca^2 ]i、主动脉平滑肌^45Ca静息内流均降低；④离体情况下ATⅡ能使SHR、WKY主动脉平滑肌^45Ca静息内流及淋巴细胞[Ca^2 ]i增加，ACEI使以上指标下降。结论：ACEI能有效逆转高血压血管重构现象，其作用可能同有效纠正血管平滑肌细胞内皮细胞钙超负荷及调节异常细胞内游离钙代谢有关。     

Comparison of the effects of telmisartan and ramipril on cerebral arteriolar inward remodeling in spontaneously hypertensive rats

AIM: The goal of this study was to compare the effects of anangiotensin Ⅱ receptor (AT1) blocker (ARB), telmisartan, with those of an angiotensin-converting enzyme inhibitor (ACEI),ramipril, on cerebral arteriolar structure and mechanics in spontaneously hypertensive rats (SHR). METHODS: Experiments were performed in 6 month-old Wistar Kyoto rats (WKY, n=16) and age-matched SHR that were untreated (SHR,n=16) or treated     

High on clopidogrel treatment platelet reactivity is frequent in acute and rare in elective stenting and can be functionally overcome by switch of therapy

The benefit of adjusted antiplatelet therapy in patients with myocardial infarction after primary percutaneous coronary intervention is not well elucidated. We aimed to identify patients with high on treatment platelet reactivity and to gradually adjust antiplatelet therapy.