ACE inhibitors reduce fecundity in the mosquito,Anopheles stephensi

Angiotensin-converting enzyme (ACE) is a dipeptidyl carboxypeptidase, which cleaves dipeptides and, in some instances, dipeptide or tripeptide amides from the C-terminus of regulatory peptides (e.g. angiotensin I, bradykinin and substance P). The expression of ACE is highly regulated in insects, where it is thought to have a role in the metabolism of peptide hormones involved in regulating reproduction. After a blood meal, ACE activity in the female mosquito Anopheles stephensi, increases four-fold with much of the enzyme finally accumulating in the ovary. In the present study, we have studied the effect on reproduction of adding two selective inhibitors of ACE, captopril and lisinopril, to the blood meal. Both ACE inhibitors reduced the size of the batch of eggs laid by females in a dose-dependent manner, with no observable effects on the behaviour of the adult insect. The almost total failure to lay eggs after feeding on either 1 mM captopril or 1 mM lisinopril, did not result from interference with the development of the primary follicle, but was due to the inhibition of egg-laying. Since very similar effects on the size of the egg-batch were observed with two selective ACE inhibitors, belonging to different chemical classes, we suggest that these effects are mediated by the selective inhibition of the induced mosquito ACE, a peptidase probably involved in the activation/inactivation of a peptide regulating egg-laying activity in A. stephensi.     

赖诺普利对血管成形术后平滑肌细胞增殖影响的研究

为研究赖诺普利对血管成形术后平滑肌细胞（ＳＭＣ）增殖的影响,用体外血管平滑肌细胞培养及氚标记胸腺嘧啶核苷（３Ｈ－ＴｄＲ）掺入技术,观察了不同浓度赖诺普利（１～２０μｇ／ｍｌ）对培养的球囊血管成形术后的兔髂动脉ＳＭＣ增殖情况的影响。结果表明：加入赖诺普利后ＳＭＣ对３Ｈ－ＴｄＲ的摄取及细胞计数明显比对照组低（Ｐ＜０．０１或Ｐ＜０．０５）,各浓度组均有作用,浓度越高作用越明显。提示赖诺普利可抑制血管成形术后平滑肌细胞的增殖,有预防血管成形术后再狭窄的作用。     

Blockade of angiotensin AT1a receptor signaling reduces tumor growth,angiogenesis, and metastasis

It was reported that angiotensin II stimulates angiogenesis in vivo, and angiotensin-converting enzyme (ACE) inhibitors inhibit angiogenesis. We found that an AT1-receptor (AT1-R) antagonist, TCV-116, inhibited tumor growth, tumor-associated angiogenesis, and metastasis in a murine model. Tumor growth of Sarcoma 180 (S-180) cells and of fibrosarcoma (NFSA) cells was strongly inhibited by administration of TCV-116 in the diet at a dose of approximately 100 mg/kg/day. This reduction was accompanied with a marked reduction in tumor-associated angiogenesis. The same treatment also reduced the lung metastasis of intravenously injected Lewis lung carcinoma cells. These effects of TCV-116 were equivalent to those of the ACE inhibitor, lisinopril. In S-180 and NFSA tumor tissues, ACE and AT1a receptor (AT1a-R) mRNAs were expressed when assessed with RT-PCR. AT1b receptor and AT2 receptor, however, were not detected. Immunoreactive AT1-R was detected mainly on the neovascularized vascular endothelial cells in which expression was reduced by TCV-116 and lisinopril. These results suggested that TCV-116 inhibits the angiogenesis, growth, and metastasis of tumors highly dependent on AT1a-R blockade. Blockade of AT1a-R signaling may therefore become an effective novel strategy for tumor chemoprevention.     

赖诺普利联合坎地沙坦治疗心力衰竭合并原发性高血压(英文)

目的:观察和评价赖诺普利联合坎地沙坦治疗心力衰竭(HF)合并原发性高血压(EH)的疗效。方法:将我院收治的EH合并HF患者69例,在给予个体化治疗的基础上随机分为:A组赖诺普利治疗组,B组坎地沙坦治疗组,C组赖诺普利和坎地沙坦联合治疗组,三组疗程均为8周。观察治疗前后的血压、心功能分级、BNP水平、心脏彩色多普勒及肝肾功检查。结果:与对照组比较,联合组的总有效率明显增高,差异有统计学意义;治疗前后所有患者肝肾功能等生化指标未见明显变化。结论:赖诺普利与坎地沙坦联合治疗心力衰竭合并原发性高血压的疗效明显优于单用赖诺普利或坎地沙坦的疗效,且安全性好,值得广泛推广和应用。     

赖诺普利联合坎地沙坦治疗心力衰竭合并原发性高血压

目的：观察和评价赖诺普利联合坎地沙坦治疗心力衰竭（HF）合并原发性高血压（EH）的疗效。方法：将我院收治的EH合并HF患者69例,在给予个体化治疗的基础上随机分为：A组赖诺普利治疗组,B组坎地沙坦治疗组,C组赖诺普利和坎地沙坦联合治疗组,三组疗程均为8周。观察治疗前后的血压、心功能分级、BNP水平、心脏彩色多普勒及肝肾功检查。结果：与对照组比较,联合组的总有效率明显增高,差异有统计学意义;治疗前后所有患者肝肾功能等生化指标未见明显变化。结论：赖诺普利与坎地沙坦联合治疗心力衰竭合并原发性高血压的疗效明显优于单用赖诺普利或坎地沙坦的疗效,且安全性好,值得广泛推广和应用。     

Effect of Acacia gum on blood pressure in rats with adenine-induced chronic renal failure

Chronic renal failure (CRF) occurring naturally in patients or induced by subtotal nephrectomy in rats induces several alterations in the cardiovascular system (CVS). However, the effect of chemically induced CRF in rats on the CVS is less well known. We induced CRF in rats by feeding adenine (0.75%, w/w, four weeks) and investigated the effect of the ensuing CRF on the systolic and diastolic blood pressure (BP) and heart rate (HR). Further, we investigated the effect of giving acacia gum (AG, 10%, w/v) in the drinking water concomitantly with adenine on the above parameters. AG has been previously shown to ameliorate the severity of CRF in humans and rats. We confirmed here that adenine-induced CRF significantly increased the plasma concentrations of urea and creatinine, and reduced creatinine clearance. Additionally, it significantly increased both systolic and diastolic BP, with no significant effect on HR. Both of these actions were significantly mitigated by AG treatment. The antihypertensive angiotenisn-converting enzyme inhibitor lisinopril (10 mg/kg) was given by gavage to rats concomitantly with adenine, significantly reduced the rise in blood pressure induced by adenine. In conclusion, adenine-induced CRF in rats significantly increased BP, and this was significantly mitigated by administration of AG. Possible mechanisms of these changes and the protective effect of AG will be investigated.     

Lisinopril和Losartan对乳鼠心脏成纤维细胞AT1受体基因表达水平和ACE活力的影响

为了解两种降压药物 -血管紧张素转换酶 (angiotensin converting enzyme,ACE)抑制剂(lisinopril)和血管紧张素 型受体 (AT1 R)拮抗剂 (losartan)在心脏间质组织中的作用 ,进行了药物对乳鼠心脏成纤维细胞 AT1 R基因表达和血管紧张素转换酶活力影响的实验 .用 RT- PCR方法检测体外培养乳鼠心脏成纤维细胞 AT1 R基因的表达 .结果显示 ,losartan在 1 0 -7～ 1 0 -4 mol/L浓度范围内对心肌成纤维细胞 AT1 R基因表达有激活作用 ,其中 1 0 -5mol/L浓度激活作用最强 ;1 0 -5mol/L losartan对 AT1 R基因表达呈现明显的时间依赖性变化 ,当加入 1 h后 ,AT1 R基因表达量增加 2倍 ,随后出现一过性下降 ,2 4 h时回升并维持在一较高水平 .与 losartan相比 ,lisinopril对 AT1 R基因的表达无明显影响 .酶活实验结果显示 ,lisinopril明显抑制心肌成纤维细胞中的ACE活力 ,随时间延长 ,酶活力逐渐恢复 (1 2 .6× 1 0 -3 U/mg) ;而 losartan则对酶活力的影响不明显 ,仅是在 1 2 h后 ,ACE活力才略有升高 .实验结果证明 ,在心脏成纤维细胞中存在有 ACE和AT1 R,并且后者受 losartan以浓度和时间依赖方式的调节 .     

Synthesis and evaluation of molecularly imprinted polymers for enalapril and lisinopril, two synthetic peptide anti-hypertensive drugs

Molecularly imprinted polymers (MIPs) for the recognition of enalapril and lisinopril were prepared using 4-vinylpyridine as the functional monomer. Following thermal polymerisation the resulting materials were crushed, ground and sieved. First generation MIPs were produced in protic polar porogenic solvents (mixture of methanol (MeOH) and acetonitrile (ACN)). These MIPs were used and validated as sorbents for solid phase extraction and binding assays. Second generation MIPs were produced with polar aprotic porogenic solvent (DMSO). These polymers were packed in HPLC columns in order to investigate their molecular recognition properties in a dynamic mode. The study of the mobile phase composition included two major parameters: organic modifier content and pH value. Retention factors illustrate selective binding of the template from the imprinted polymers, compared to structurally related compounds.     

赖诺普利与贝那普利治疗高血压合并脑卒中的疗效及对血清ADMA水平的影响

目的:探讨赖诺普利与贝那普利治疗高血压合并脑卒中的疗效及对血清非对称性二甲基精氨酸(ADMA)水平的影响,以期为高血压合并脑卒中的治疗提供指导。方法:选取2014年1月-2016年3月在我院确诊并接受治疗的高血压合并脑卒中246例,按随机数字表法将患者随机分为研究组、对照组和常规组,每组各82例。常规组采用基础治疗,研究组采用基础治疗联合赖诺普利治疗,对照组采用基础治疗联合贝那普利治疗。比较3组患者治疗前后血压参数、血清ADMA和Hcy水平、治疗效果和不良反应。结果:治疗前三组患者的血压参数(SBP、DBP和PP)、血清ADMA和Hcy水平、m RS评分均无显著差异;治疗后三组患者上述指标水平较治疗前均显著降低(P0.05),且研究组患者指标水平明显低于对照组和常规组(P0.05)。研究组治疗有效率明显高于对照组和常规组,对照组治疗有效率明显高于常规组,上述差异均具有统计学意义(P0.05)。三组患者不良反应率无显著差异(P0.05)。结论:赖诺普利和贝那普利均能有效降低高血压合并脑卒中患者血压水平,改善血管内皮功能,疗效显著;但赖诺普利的效果要比贝那普利更好,更值得临床推广。