Beneficial effect of ACE inhibitor in congestive heart failure

The effects of captopril, an angiotensin-converting enzyme inhibitor, on congestive heart failure (CHF) were investigated in animal and clinical studies. Congestive heart failure was induced in rats by a combination of pressure and volume overload. Cardiac pressure overload was induced by constricting one renal artery (Goldblatt rat) and volume overload was induced by aorto-caval fistula. Captopril (100 mg/kg/day) was then administered for 14 weeks. Isometric contraction was assessed using isolated left ventricular papillary muscles. The maximum developed tension and the maximum rate of increase in tension (dT/dtmax) were decreased in untreated rats with CHF and improved in captopriltreated rats. The left ventricular myosin isoenzyme pattern was shifted towards V3 in untreated rats with CHF, and was shifted back towards V1 in the captopril-treated rats. In the clinical study, captopril (37.5–75 mg/day) was administered to patients with cardiomyopathy for 12 months. There was no effect on left ventricular mass in hypertrophic cardiomyopathy, although systolic anterior motion of the mitral valve disappeared in one patient. In dilated cardiomyopathy, however, left ventricular mass tended to decrease. These results indicate that captopril has a beneficial effect in congestive heart failure.     

Superoxide dismutase activity of the captopril-iron complex

With an assay that generates superoxide anion radicals without the intervention of metal ions we investigated the antioxidant properties of captopril, an angiotensin-converting enzyme inhibitor with a sulfhydryl group. Under these conditions, increasing concentrations of the drug were seen not to scavenge O· ₂ ^– directly. However, a combination of captopril and iron could bring about the breakdown of the superoxide anion; a result that may help to understand the free radical-scavenging properties of captopril.     

Atorvastatin and losartan may upregulate renalase activity in hypertension but not coronary artery diseases: The role of gene polymorphism

The aim is to explore the treatment effect of coronary artery disease (CAD) and hypertension on plasma levels of renalase activity and also the possible association of renalase rs10887800 gene polymorphism with CAD and hypertension. A total of 286 patients who received coronary angiography were included in the study. Subjects were divided into four groups including (1) hypertensive with no CAD (H-Tens, n = 60); (2) CAD with hypertension (CAD + H-Tens, n = 71); (3) CAD with no hypertension (CAD, n = 61); and (4) nonhypertensive with no CAD as a control group (Con, n = 69). The plasma renalase activity was measured using the Amplex Red Monoamine Oxidase Assay Kit. Renalase rs10887800 single-nucleotide polymorphisms (SNPs) were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Atorvastatin (P = 0.005), losartan (P < 0.001), and captopril (P = 0.001) were administered significantly more in case groups compared with the Con group. Significant higher and lower levels of renalase activity were observed in H-Tens and CAD patients compared with control subjects (P < 0.001 for both comparisons). Furthermore, no significant differences were obtained in the risk or protective effects of renalase rs10887800 SNP against hypertension and/or CAD in both recessive and dominant genetic models (P > 0.05). According to the findings of the present study, atorvastatin and losartan therapy assumes considerable significance in alleviating hypertension, but not CAD, by increasing the renalase activity. Furthermore, it was found that renalase rs10887800 is less likely a predisposing factor for susceptibility to hypertension and/or CAD in an Iranian southeast population.     

The angiotensin converting enzyme inhibitor captopril reduces oviposition and ecdysteroid levels in Lepidoptera

The role of angiotensin converting enzyme (ACE, peptidyl dipeptidase A) in metamorphic- and reproductive-related events in the Egyptian cotton leafworm, Spodoptera littoralis (Lepidoptera, Noctuidae) was studied by using the selective ACE inhibitor captopril. Although oral administration of captopril had no effect on larval growth, topical administration to new pupae resulted in a large decrease of successful adult formation. Oviposition and overall appearance of adults emerging from treated larvae did not differ significantly from those emerging from non-treated larvae. In contrast, topical or oral administration of captopril to newly emerged adults caused a reduction in oviposition. By evaluating the effect of captopril on ecdysteroid titers and trypsin activity, we revealed an additional physiological role for ACE. Captopril exerted an inhibitory effect on ecdysteroid levels in female but not in male adults. Larvae fed a diet containing captopril exhibited increased trypsin activity. A similar captopril-induced increase in trypsin activity was observed in female adults. In male adults, however, captopril elicited reduced levels of trypsin activity. Our results suggest that captopril downregulates oviposition by two independent pathways, one through ecdysteroid biosynthesis regulation, and the other through regulation of trypsin activity. Apparently, fecundity is influenced by a complex interaction of ACE, trypsin activity, and ecdysteroid levels.     

血管紧张素转换酶抑制剂和醛固酮受体阻断剂对钙超载大鼠心功能的影响

目的:观察血管紧张素转换酶抑制剂(ACEI)和醛固酮(ALDO)受体阻断剂(spironolactone,安体舒通)对钙超载大鼠心功能的影响,以探讨钙超载引起心功能降低和心肌损伤的机制。方法:维生素D3加尼古丁诱导心肌钙超载,放射免疫法测定心肌组织AngⅡ和ALDO含量,Powerlab仪测定心功能,原子吸收测定心肌和血管钙含量,生化法测定心肌MDA和conjugated diene变化,自动生化分析仪测定血浆LDH和CPK含量。结果:心肌钙超载后,心肌和血管钙含量较对照组分别增加3.2和5.8倍,LVdp/dtmax和LVdp/dtmin分别降低27%和34%,LVESP和LVEDP增加42%和32%;心肌MDA和conjugated diene增加22%和68%;血浆LDH和CPK增加4.5和3.1倍(均P<0.01)。运用ACEI和ALDO受体阻断剂可缓解上述指标变化,与钙超载组相比,心肌钙含量分别低44%和39%,主动脉钙含量也低57%和34%,MDA低20%和30%,conjugated diene低44%和35%,LDH、CPK分别减少28%和34%、20%和27%(均P<0.01)。结论:心肌钙超载可以导致心功能下降和心肌损伤,运用ACEI和ALDO受体阻断剂可以减轻心肌钙超载和改善心功能,心肌损伤程度减轻。     

The influence of cell growth media on the stability and antitumour activity of methionine enkephalin.

Studies with cultured tumour cell lines are widely used in vitro to evaluate peptide-induced cytotoxicity as well as molecular and biochemical interactions. The objectives of this study were to investigate the influence of the cell culture medium on peptide metabolic stability and in vitro antitumour activity. The degradation kinetics of the model peptide methionine enkephalin (Met-E, Tyr-Gly-Gly-Phe-Met), demonstrated recently to play an important role in the rate of proliferation of tumour cells in vitro and in vivo, were investigated in cell culture systems containing different amounts of fetal bovine serum (FBS). The influence of enzyme inhibitors (bestatin, captopril, thiorphan) on the Met-E degradation was also investigated. The results obtained in the Dulbecco's modified Eagle medium containing 10% FBS indicated a rapid degradation of Met-E (t(1/2) = 2.8 h). Preincubation of the medium with a mixture of peptidase inhibitors reduced the hydrolysis of Met-E, as shown by the increased half-life to 10 h. The in vitro activity of Met-E against poorly differentiated cells from lymph node metastasis of colon carcinoma (SW620) and human larynx carcinoma (HEp-2) cells was determined. Tumour cells were grown for 3 weeks prior to the experiment in a medium supplemented with 10%, 5% or 2% FBS. Statistically significant to mild or no suppression of cell proliferation was observed in all cultures. In both cell lines, a significant suppression of cell growth by a combination of peptidase inhibitors and Met-E, compared with cells exposed to the peptide alone and cells grown in the absence of Met-E, was observed. This study indicated that caution must be exercised in interpreting the antiproliferative effects of peptide compounds in conventional drug-response assays.     

Role of cardiac renin-angiotensin system in the development of pressure-overload left ventricular hypertrophy in rats with abdominal aortic constriction

Possible involvement of cardiac renin-angiotensin system (RAS) in pressure overload induced left ventricular hypertrophy (LVH) was investigated. Rats were subjected to abdominal aortic constriction (AAC) and examined the effects of 4 weeks treatments with an angiotensin converting enzyme (ACE) inhibitor, captopril and a vasodilator, hydralazine on haemodynamics and ventricular RNA, DNA, protein and myosin isoform pattern in sham and hypertrophied rats. AAC increased the mean arterial pressure (MAP) and systolic blood pressure (SBP), and resulted in increased left ventricle/body weight ratio, LV thickness, RNA and protein content, however total DNA was not changed. The expression of fetal isogene, -myosin heavy chain (-MHC), was markedly enhanced where as u.-MHC was reduced. High-dose captopril (100 mg/kg p.o.,) significantly prevented the increase in haemodynamics, development of LVH, LV remodeling, increase in total protein, RNA and antithetical expression of myosin isoforms. Hydralazine (15 mg/kg p.o.,), did not modulate hypertrophic changes and low-dose captopril (1.5 mg/kg p.o.,) which has not produced any marked fall in MAP and SBP also modulated favourably the development of LVH and its biochemical markers. Thus, the prevention of the development of LVH and induction of -MHC by non-hypotensive doses of captopril may be related to the blockade of intracardiac production of angiotensin II rather than circulating system. These results suggest that cardiac RAS may play an important role in pressure overload induced LVH.     

Development of a new procedure for the determination of captopril in pharmaceutical formulations employing chemiluminescence and a multicommuted flow analysis approach

This paper describes a new technique for the determination of captopril in pharmaceutical formulations, implemented by employing multicommuted flow analysis. The analytical procedure was based on the reaction between hypochlorite and captopril. The remaining hypochlorite oxidized luminol that generated electromagnetic radiation detected using a homemade luminometer. To the best of our knowledge, this is the first time that this reaction has been exploited for the determination of captopril in pharmaceutical products, offering a clean analytical procedure with minimal reagent usage. The effectiveness of the proposed procedure was confirmed by analyzing a set of pharmaceutical formulations. Application of the paired t‐test showed that there was no significant difference between the data sets at a 95% confidence level. The useful features of the new analytical procedure included a linear response for captopril concentrations in the range 20.0–150.0 µmol/L (r = 0.997), a limit of detection (3σ) of 2.0 µmol/L, a sample throughput of 164 determinations per hour, reagent consumption of 9 µg luminol and 42 µg hypochlorite per determination and generation of 0.63 mL of waste. A relative standard deviation of 1% (n = 6) for a standard solution containing 80 µmol/L captopril was also obtained. Copyright © 2015 John Wiley & Sons, Ltd.     

Real-time changes of the local vasoactive peptide systems (angiotensin,endothelin) in the bovine corpus luteum after induced luteal regression

There is evidence that angiotensin II (Ang II) and endothelin-1 (ET-1) may interact in an additive or synergistic way during luteal regression. The aim of the study was to investigate real time changes in luteal tissue of angiotensin and endothelin system members in mRNA expression, tissue concentrations, tissue localization, and ACE (angiotensin converting enzyme) antagonist application after prostaglandin F(2alpha) (PG) induced (days 8-12) luteal regression in cow. Corpora lutea (CL) were collected by transvaginal ovaryectomy before and 2, 4, 12, 24, 48, and 64 hr (n = 5/time point) after PG injection. ACE mRNA expression (RT-PCR) increased continuously and peaked at 12, 24 hr; ECE-1 (endothelin converting enzyme) peaked at 12 hr, and both peptides in tissue (Ang II and ET-1) increased significantly and peaked at 24 hr. The expression of receptors for Ang II (AT1R and AT2R) did not change in contrast to ET receptors (ETR-A and ETR-B), which were up-regulated. Localization in tissue revealed very weak staining for Ang II and ET-1 before PG application followed by a clear increase of staining predominantly in large luteal cells, but also in endothelial cells. In two experiments, the attempt was made to block ACE by the antagonist captopril with two different doses. In both experiments with captopril, progesterone levels were not significantly different from controls. Ang II alone seems to be not essential for functional luteolysis in bovine system. In conclusion, the results suggest that both Ang II and ET-1 are in parallel up-regulated during luteal regression and may act as vasoconstrictors during functional luteolysis, but also as apoptosis inducer during functional/structural luteolysis.     

一氧化氮改变肾性高血压大鼠主动脉功能

探讨一氧化氮（ＮＯ）对二肾一夹（２Ｋ１Ｃ）肾性高血压大鼠主动脉功能的影响。实验分为５组：假手术、２Ｋ１Ｃ、卡托普利（ｃａｐｔｏｐｒｉｌ）、ＮＡＭＥ（Ｎω－Ｎｉｔｒｏ－Ｌ－ａｒｇｉｎｉｎｅ ｍｅｔｈｙｌ ｅｓｔｅｒ）和精氨酸组。结果显示：在２Ｋ１Ｃ组,大鼠手术后４周的平均动脉压显著升高,主动脉对４Ｃｈ的舒张反应明显减弱,对苯肾上腺素收缩反应明显增强,主动脉壁环鸟苷酸（ｃＧＭＰ）含量显著减少。卡托谱利