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AIM:In this study, the rat lung injury model was induced by ammonium chloride for studying the effect of imidapril on blood gas, serum TNF-α, IL-6 and MDA concentrations, and AngⅡand CD54 protein expression in rat lung tissue.METHODS:Male rats were randomly divided into 3 groups:control group, lung injury model group and drug group.The rats in control group were given saline (2 mL/kg), while the rats in lung injury model group were given 6% ammonium chloride (2 mL/kg).In drug group, imidapril (3 mg· kg-1· d-1) was given to the rats once daily for 1 week by intragastric gavage after given 6%ammonium chloride.On the 7th day, the rats were anesthetized with 2% so-dium pentobarbital.Abdominal aorta blood, venous blood and lung tissue were collected.The blood gas indexes and serum TNF-α, IL-6 and MDA concentrations were determined.The lung tissues were fixed and sliced, and the expression of AngⅡ and CD54 proteins was detected by immunohistochemistry.RESULTS: The PaCO2 increased in lung injury model group compared with control group and drug group (P<0.05).The expression of AngⅡand CD54, and the concentrations of TNF-α, IL-6 and MDA also increased significantly ( P<0.01) in model group.Pulmonary edema, inflammation, alveo-lus congestion, hemorrhage and hyperplasia in model group were obvious compared with control group and drug group. CONCLUSION:Imidapril improves blood gas indexes, and reduces lipid peroxidation and inflammatory responses in the rats with lung injury induced by ammonium chloride.
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Objective:To evaluate the inhibitory effect of 5 Chinese herbal medicinal ingredients baicalin, andrographolide, hes-peridin, polyphenols and daidzein on the activity of carboxylesterase 1 (CES1) and carboxylesterase 2 (CES2). Methods: The spe-cial probes respectively for CES1 and CES2, namely imidapril and CPT-11, imidaprilat and SN-38, were used to investigate the poten-tial effect of the above drugs on CES1 and CES2 in rat liver microsomes incubation system. Results:Compared with that in the control group, the activity of CES1 and CES2 was not significantly influenced by the above 5 Chinese herbal medicinal ingredients ( P <0. 05). Conclusion:Baicalin, andrographolide, hesperidin, polyphenols and daidzein exhibit no inhibitory effect against CES1 and CES2, and further studies should be conducted to confirm the effect in vivo.
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Simple, accurate, sensitive and validated UV spectrophotometric and chemometric methods were developed for the determination of imidapril hydrochloride (IMD) in the presence of both its alkaline (AKN) and oxidative (OXI) degradation products and in its pharmaceutical formulation. Method A is the fourth derivative spectra (D4) which allows the determination of IMD in the presence of both AKN and OXD, in pure form and in tablets by measuring the peak amplitude at 243.0 nm. Methods B, C and D, manipulating ratio spectra, were also developed. Method B is the double divisor-ratio difference spectrophotometric one (DD-RD) by computing the difference between the amplitudes of IMD ratio spectra at 232 and 256.3 nm. Method C is the double divisor-first derivative of ratio spectra method (DD-DR1) at 243.2 nm, while method D is the mean centering of ratio spectra (MCR) at 288.0 nm. Methods A, B, C and D could successfully determine IMD in a concentration range of 4.0-32.0 mg/mL. Methods E and F are principal component regression (PCR) and partial least-squares (PLS), respectively, for the simultaneous determination of IMD in the presence of both AKN and OXI, in pure form and in its tablets. The developed methods have the advantage of simultaneous determination of the cited components without any pre-treatment. The accuracy, precision and linearity ranges of the developed methods were determined. The results obtained were statistically compared with those of a reported HPLC method, and there was no significant difference between the proposed methods and the reported method regarding both accuracy and precision.
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Objective Utilizing the characters of pyrrolidine dithiocarbamate known as a specific inhibitor of NF‐κB and imidapril known as a specific inhibitor of angiotensin converting enzyme ,this study was to initially investigate the relationship between NF‐κBp65 and AngⅡ during the process of myocardial ischemia reperfusion injury .Methods Rat models of myocardial ischemia reper‐fusion injury were successfully established .The observation point is 60 min of reperfusion after 30 min(I30 min R60 min ) ischemia ,the DNA activate of NF‐κBp65 was detected by ELISA ;the content of AngⅡ in blood plasma and cardiac were determined by radioim‐munoassay .We pretreated with pyrrolidine dithiocarbamate ,imidapril ,and both of them to observe changes of the same indexs .Re‐sults Compared with I30 min R60 min ,Pyrrolidine dithiocarbamate ,Imidapril and pyrrolidine dithiocarbamate add imidapril could all ob‐viously inhibit NF‐κBp65 activation and depress the content of Ang Ⅱ in blood plasm and cardiac ,the pyrrolidine dithiocarbamate add imidapril was most obviously .Conclusion During the process of myocardial ischemia‐reperfusion injury ,NF‐κBp65 had been activated ,and the content of Ang Ⅱ in blood plasm and cardiac had increased .NF‐κBp65 and AngⅡ could influence and promote each other during myocardial ischemia reperfusion injury .
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Objective To define the heterogeneous changes of ion channels in the noninfarcted myocardium after myocardial infarction in rabbit and effects of imidapril.Mehods Rabbits with left coronary artery ligation were prepared and allowed to recover for 8 wk.Myocytes were isolated from subendocardial,midmyocardial and subepicardial regions of the noninfarcted left ventricular free wall.Ion currents were recorded with whole-cell patch clamp way.Results The densities of the transient outward K+ currents (I to) and the inward rectifier K+ currents (I K1) were greatly reduced in midmyocardium and subepicardium while two currents reduced gently in subendocardium.The densities of the delayed rectifier K+ currents (I K) were reduced in noninfarcted three layers similarly.Imidapril could reverse the changes of membrane currents in healed myocardial infarction cells and depress the dispersion of repolarization.Conclusions The heterogeneities of K currents are enhanced in noninfarcted area.Normalization of heterogeneous changes of repolarization after treatment with imidapril was observed.
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@#ObjectiveTo investigate the effects of imidapril on the transmural dispersion of repolarization of the noninfarcted myocardium of rabbits after myocardial infarction. MethodsRabbits with left coronary artery ligation were prepared and allowed to recover for 8 weeks. Monophasic action potentials of three layers myocardium in the noninfarcted myocardium in vivo were recorded. Myocytes were isolated from subendocardial, midmyocardial and subepicardial regions of the noninfarcted left ventricular wall and action potentials were recorded using whole-cell patch clamp technique. ResultsCompared with sham group, the monophasic action potential duration (MAPD90) of three layers myocardium were all prolonged. Prolongation of MAPD_ 90 of midmyocardial cell was the most striking and ventricular fibrillation threshold (VFT) was decreased. After treatment with imidapril, the transmural dispersion of repolarization (TDR) decreased and the VFT enhanced. ConclusionImidapril reduced the transmural dispersion of repolarization of noninfarcted area in rabbits after myocardial infarction, which may contribute to its antiarrhythmic efficacy.
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Objective To delineate the speculation that triple combination of small doses of calcium antagonist (levoamlodipine),the ACEI(imidapril)and the ARB(candesartan)may exert more significantly effect on mi- croalbuminuria(MAU)in patients with type 2 diabetes mellitus and hypertension.Methods One hundred sixty ca- ses of consecutive patients with type 2 diabetes mellitus and hypertension were randomized to receive following vari- ous combinations:amlodipine 2.5 mg/candesartan 4 mg(n=40),candesartan 4 mg/imidapril 5 mg(n=40);imidapril 5 mg/amlodipine 2.5 mg(n=40),and amlodipine 2.5 mg/candesartan 4,mg plus imidapril 5 mg(n=40).The changes in blood pressure and MAU were determined before and after treatment.Results Four combinations of treatment all significantly lowered BP(P
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We describe a patient with hyponatremia induced by the use of angiotensin-converting enzyme (ACE) inhibitor; imidapril HCl. Although the mechanism of severe hyponatremia due to ACE inhibitor is not clear, it is conceivable that ACE inhibitor therapy may complicate the syndrome of inappropriate secretion of antidiuretic hormone and induce hyponatremia. In addition, the possibility should be considered that hyponatremia in our patient is a presumptive interaction between oxcarbazepine and imidapril HCl.
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Humans , Angiotensins , Hyponatremia , Peptidyl-Dipeptidase AABSTRACT
Objective To certify insuline resistance in nonobese patients with essential hypertension(EH) and observe effect of imidapril.Methods An oral glucose tolerance test(OGTT) and insulin releasing test(IRT) were performed on 40 nonobese EH patients before and after imidapril treatment,the plasma levels of glucose and insulin were tested and compared with those of 16 normal subjects.Results The insuline level of fasting or 30,60,120 min after OGTT were significantly higher than those in normal group(P
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Imidapril(Tanatril(R)), a newly developed ACE inhibitor, has been used to treat hypertension and congestive heart failure. This study was designed to assess the antihypertensive effect and safety of Imidapril(Tanatril(R)) in patient with essential hypertension. 5-10mg of imidapril(Tanatril(R)) was administered once day in 30 patients with essential hypertension and followed up to 8 weeks. We tested the drug's effectiveness, safety, and the incidence of imidapril induced dry coughs. After 8 weeks of treatment with Imidapril, 76.2%(16/21) of patient showed lowered blood pressure and 47.6% showed normal blood pressure. The overall incidence of adverse effects was 33.3%(7/21). and among these adverse effects. dry cough was shown in only 9.5%. Thus, concluded that imidapril(Tanatril(R)) is as safe and effective as other ACE inhibitors. especially with imidapril showing very little incidence of dry cough compared to other ACE inhibitors.
Subject(s)
Humans , Angiotensin-Converting Enzyme Inhibitors , Blood Pressure , Cough , Heart Failure , Hypertension , IncidenceABSTRACT
BACKGROUND: Imidapril is a long-acting angiotensin converting enzyme inhibitor, which has been demons-trated to be effective in reducing blood pressure. The purpose of this study is to compare the antihypertensive efficacy, safety and tolerability of imidapril and enalapril in patients with stage 1 to 2 essential hypertension. METHODS: In this double-blind, double-dummy, randomized, parallel study, the efficacy, safety and tolerability of once-daily imidapril versus once-daily enalapril were evaluated in 84 patients with stage 1 - 2 hypertension during 8 weeks. If antihypertensive response was insufficient after 4 week treatment period, the dosage for both study drugs doubled until the end of study. RESULTS: Data from 84 patients who completed the study were eligible for per-protocol analysis. An adequate antihypertensive effect was observed in 47.6% (20/42) in the imidapril group and in 23.8% (10/42) in enalapril group. There was statistically significant difference between the two treatments in the percentage of patients achieving a "reduced blood pressure". The pulse rate did not changed in both groups. Safety profiles were similar between treatments. CONCLUSION: In patients with mild to moderate hypertension, the imidapril group showed better response with regard to antihypertensive effect. Both imidapril and enalapril were well tolerated with similar safety profiles.
Subject(s)
Humans , Blood Pressure , Enalapril , Heart Rate , Hypertension , Peptidyl-Dipeptidase AABSTRACT
BACKGROUND AND OBJECTIVES: Imidapril, one of the ACE inhibitor, has been used to treate hypertension, congestive heart failure, diabetes mellitus and renal disease. ACE inhibitor, however often causes dry cough and this adverse effect affects the compliance rate negatively. This report aimed to examine the incidence rate of coughing caused by Imidapril treat-ment. And we compared the results with the incidence and tendency of dry cough caused by the other ACE inhibitors. MATERIALS AND METHOD: This study enrolled 38 patients who followed up at internal medicine and took Imidapril from the period of May 9, 1997 to December 17, 1997. We tested its effectiveness, safety and tolerance. The initial dosage of it was 5mg/day and the maximum dosage according to blood pressure was 10mg/day for 8 weeks. The tendency and the incidence of dry cough have been analyzed and compared with recently published Korean reports. RESULTS: The 5 mg dosage of Imidapril showed 68.1% in lowering blood pressure rate and it went up to 81.8% during the 8 weeks treatment perriod. The blood pressure regularity rate was 36.3% after the 8 weeks treatment. The overall rate of adverse effect occurrence was 26.1% (6/23) and 8.7% of them were likely to cough. One of the patients who showed nausea stopped medication. The recent articles reported that the incidence of dry cough had been reduced: Enalapril (33.8%), Fosinopril (16%), Ramipril (15%), Imidapril (7.8 - 8.7%), Losartan (4.3%). CONCLUSION: Imidapril is as safe and effective as other ACE inhibitors. Various ACE inhibitors that were newly developed show their effectiveness in lessening incidence rate of dry cough, and Imidapril is thought to be an excellent drug for this matter. Even though Losartan shows the lowest incidence rate of dry cough, it needs to more regular usages since it is still on the stage of its medical adaptation.