Evaluation of a miniature mass spectrometer based point-of-care-test method for direct analysis of amlodipine and benazepril in whole blood.

A miniature mass spectrometer (mMS) based point-of-care testing (POCT) method was evaluated for on-site detecting the hypertension drugs, amlodipine and benazepril. The instrument parameters, including voltage, ISO1, ISO2, and CID, were optimized, under which the target compounds could be well detected in MS2. When these two drugs were injected simultaneously, the mutual ionization inhibition and mutual reduction between amlodipine and benazepril were evaluated. This phenomenon was severe on the precursor ions but had a small impact on the product ions, thus making this POCT method suitable for analysis using product ions. Finally, the method was validated and applied. The blood samples from patients were tested one hour after oral administration of the drugs (20 mg), and the benazepril was quantitatively analyzed using a standard curve, with detected concentrations ranging from 190.6 to 210 µg L-1 and a relative standard deviation (RSD) of 8.6 %. In summary, amlodipine has low sensitivity and can only be detected at higher concentrations, while benazepril has high sensitivity, good linearity, and even meets semi-quantitative requirements. The research results of this study are of great clinical significance for monitoring blood drug concentrations during hypertension medication, predicting drug efficacy, and customizing individualized medication plans.

A Comparative Study of the Safety and Efficacy Between Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers on the Management of Hypertension: A Systematic Review.

Renin-angiotensin-aldosterone system (RAAS) inhibitors, including angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), are commonly used in the management of hypertension. High blood pressure is a vital risk factor for cardiovascular disease. This study aims to establish any significant difference in using ACEIs and ARBs in managing hypertension. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to conduct this systematic review. We searched PubMed, MEDLINE, and ScienceDirect for articles published in the last 20 years (2003 to 2023). Our search was last done on the 27th of June, 2023. Following the initial search, 8,313 articles were found on PubMed. After screening the articles selected from the databases, 10 articles examining 1,621,445 patients were selected for the final study. Three articles were identified that compared ACEI and ARB in their capacity to lower blood pressure. Six articles compared both medications' capacity to reduce cardiovascular events and mortality. Five articles were identified that compared both classes of drugs for adverse effects. This study was made to determine whether or not there is a difference between the use of ACEIs and ARBs in the treatment of hypertension. The study showed that both ACEIs and ARBs are similar in their efficacy in lowering blood pressure. However, ACEI was revealed to be superior to ARB in reducing cardiovascular events and all-cause mortality. ARB was shown to be better tolerated by patients than ACEI.

Self-Reported Utilization of International (ACVIM Consensus) Guidelines and the Latest Clinical Trial Results on the Treatment of Dogs with Various Stages of Myxomatous Mitral Valve Degeneration: A Survey among Veterinary Practitioners.

BACKGROUND: Myxomatous mitral valve degeneration is the most common canine heart disease. Several clinical trials have investigated various treatments. The latest recommendations are published in the ACVIM consensus guidelines (2019). Our study aimed to investigate how closely veterinary practitioners apply the treatment recommendations of these guidelines and the latest clinical trials. METHODS: An online survey was sent to Dutch and Belgian veterinary practices via digital channels. RESULTS: The data from 363 fully completed surveys were analyzed. For stage B1 disease, 93% recommended, correctly, no treatment. For stage B2 disease, 67% of the respondents recommended starting pimobendan as monotherapy. For chronic treatment of stage C disease, 16 different drug combinations were mentioned, but nobody recommended surgery. Only 48% of the respondents recommended the only evidence-based drug combination: a loop diuretic with pimobendan. A concerning finding was the simultaneous prescription of two loop diuretics, by 19% of the respondents. CONCLUSIONS: Treatment recommendations showed an increasing variation with more advanced disease stages from B1 through B2 to C. This reflects the increasing disagreement among the panelists who prepared the ACVIM consensus guidelines. Practitioners of our study seem to practice more evidence-based medicine than veterinary cardiologists, as it was reported in a recent survey-based study.

Comparison of two single-pill dual combination antihypertensive therapies in Chinese patients: a randomized, controlled trial.

BACKGROUND: Current hypertension guidelines recommend combination of an angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker with a calcium-channel blocker or thiazide diuretic as initial antihypertensive therapy in patients with monotherapy uncontrolled hypertension. However, to what extent these two different combinations are comparable in blood pressure (BP)-lowering efficacy and safety remains under investigation, especially in the Chinese population. We investigated the BP-lowering efficacy and safety of the amlodipine/benazepril and benazepril/hydrochlorothiazide dual therapies in Chinese patients. METHODS: In a multi-center, randomized, actively controlled, parallel-group trial, we enrolled patients with stage 1 or 2 hypertension from July 2018 to June 2021 in 20 hospitals and community health centers across China. Of the 894 screened patients, 560 eligible patients were randomly assigned to amlodipine/benazepril 5/10 mg (n = 282) or benazepril/hydrochlorothiazide 10/12.5 mg (n = 278), with 213 and 212 patients, respectively, who completed the study and had a valid repeat ambulatory BP recording during follow-up and were included in the efficacy analysis. The primary outcome was the change from baseline to 24 weeks of treatment in 24-h ambulatory systolic BP. Adverse events including symptoms and clinically significant changes in physical examinations and laboratory findings were recorded for safety analysis. RESULTS: In the efficacy analysis (n = 425), the primary outcome, 24-h ambulatory systolic BP reduction, was - 13.8 ± 1.2 mmHg in the amlodipine/benazepril group and - 12.3 ± 1.2 mmHg in the benazepril/hydrochlorothiazide group, with a between-group difference of - 1.51 (p = 0.36) mmHg. The between-group differences for major secondary outcomes were - 1.47 (p = 0.18) in 24-h diastolic BP, - 2.86 (p = 0.13) and - 2.74 (p = 0.03) in daytime systolic and diastolic BP, and - 0.45 (p = 0.82) and - 0.93 (p = 0.44) in nighttime systolic and diastolic BP. In the safety analysis (n = 560), the incidence rate of dry cough was significantly lower in the amlodipine/benazepril group than in the benazepril/hydrochlorothiazide group (5.3% vs 10.1%, p = 0.04). CONCLUSIONS: The amlodipine/benazepril and benazepril/hydrochlorothiazide dual therapies were comparable in ambulatory systolic BP lowering. The former combination, compared with the latter, had a greater BP-lowering effect in the daytime and a lower incidence rate of dry cough. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03682692. Registered on 18 September 2018.

Response and survival of dogs with proteinuria (UPC > 2.0) treated with angiotensin converting enzyme inhibitors.

BACKGROUND: Angiotensin-converting enzyme inhibitors (ACEi) are a recommended treatment for glomerular proteinuria. Frequency of response to ACEi and the association of achieving proposed urine protein-to-creatinine ratio (UPC) targets on survival is unknown. OBJECTIVES: To determine response rates to ACEi therapy and whether a positive response is associated with improved survival. ANIMALS: Eighty-five dogs with proteinuria (UPC > 2.0). METHODS: Retrospective study including dogs (UPC > 2.0) prescribed an ACEi for treatment of proteinuria. Baseline creatinine, albumin, cholesterol, UPC, and systolic blood pressure were recorded, and cases reviewed to track UPC. Treatment response was defined as achieving a UPC of <0.5 or reduction of ≥50% from baseline within 3 months. Outcome data were collected to determine overall and 12-month survival. RESULTS: Thirty-five (41%) dogs responded to ACEi treatment. Treatment response was statistically associated with both median survival time (664 days [95% confidence interval (CI): 459-869] for responders compared to 177 [95% CI: 131-223] for non-responders) and 12-month survival (79% responders alive compared to 28% non-responders). Baseline azotemia or hypoalbuminemia were also associated with a worse prognosis, with odds ratios of death at 12 months of 5.34 (CI: 1.85-17.32) and 4.51 (CI: 1.66-13.14), respectively. In the 25 dogs with normal baseline creatinine and albumin, response to treatment was associated with 12-month survival (92% responders alive compared to 54% non-responders, P = .04). CONCLUSIONS AND CLINICAL IMPORTANCE: When the UPC is >2.0, achieving recommended UPC targets within 3 months appears to be associated with a significant survival benefit. Response to treatment is still associated with survival benefit in dogs with less severe disease (no azotemia or hypoalbuminemia).

Therapeutic effect of sodium­glucose cotransporter 2 inhibitor and benazepril on diabetic nephropathic rats.

The present study aimed to compare the therapeutic effect of sodium/glucose cotransporter 2 (SGLT2) inhibitor and benazepril on diabetic nephropathy (DN) rats and provide a potential novel agent for the clinical treatment of DN. The DN model was established on rats. Animals were dosed orally with SGLT2 and benazepril daily for 4 weeks. The pathological state of renal tissues were evaluated using hematoxylin and eosin, Masson and periodic acid-Schiff staining. The change in the morphology of renal tissues was observed through transmission electron microscopy. Western blotting was utilized to determine the expression level of TGF-ß, N-terminal fragment of the B-type natriuretic peptide precursor (NT-proBNP) and matrix metalloproteinase-9 (MMP-9). The expression level of endothelin 1 (ET-1), von Willebrand factor (vWF), collagen (col)-I and α smooth muscle actin (α-SMA) in renal tissues was visualized using immunohistochemical assay. Significant pathological changes in the glomerular basement membrane, mesangial membrane, renal tubules, lumen, renal interstitial region and renal tubular epithelial cells were observed in DN rats, accompanied by increased collagen fibers. SGLT2 inhibitor treatment demonstrated more alleviatory effects on the pathological changes of renal tissues compared with benazepril. Compared with control, TGF-ß and NT-proBNP were upregulated in DN rats, accompanied by the downregulation of MMP-9, ET-1, vWF, col-I and α-SMA, which were markedly reversed by treatment with SGLT2 inhibitor and benazepril. Compared with benazepril, the effects of SGLT2 inhibitor on the expression level of TGF-ß, NT-proBNP, MMP-9, ET-1, vWF, col-I and α-SMA were more significant. Overall, SGLT2 inhibitor demonstrated an increased therapeutic effect against DN rats compared with benazepril by regulating cytokines, renal fibrosis and extracellular matrix degradation.

Retrospective evaluation of a dose-dependent effect of angiotensin-converting enzyme inhibitors on long-term outcome in dogs with cardiac disease.

BACKGROUND: Angiotensin-converting enzyme inhibitors (ACEIs) are commonly prescribed in dogs, but the ideal dosage is unknown. HYPOTHESIS/OBJECTIVES: In dogs with cardiac disease, a dose-response relationship exists for ACEIs with respect to long-term outcome. ANIMALS: One hundred forty-four dogs with cardiac disease, 63 with current or prior congestive heart failure. METHODS: Retrospective medical record review. Cox proportional hazards models were used to determine variables associated with 2-year survival or survival from first-onset congestive heart failure (CHF). RESULTS: Median initial ACEI dosage was 0.84 (interquartile range [IQR], 0.56-0.98) mg/kg/day, and 108/144 (75%) of dogs received q12h dosing. No clinically relevant changes in renal function test results, serum electrolyte concentrations, or blood pressure occurred between initial prescription of ACEI and first reevaluation (median, 14 days later). In univariable analysis, higher ACEI dose was associated with increased survival from first-onset CHF (P = .005), and within the subgroup of dogs in CHF at the time of ACEI prescription, higher ACEI dose was associated with improved survival at 2 years (P = .04). In multivariable analysis, q12h dose frequency of ACEI (hazard ratio [HR], 0.30; 95% CI, 0.10-0.88; P = .03) and higher serum potassium concentration at visit 1 (HR, 0.39; 95% CI, 0.16-0.97; P = .04) were predictive of 2-year survival. The ACEIs were well-tolerated, with only 8/144 (5.6%) dogs having ACEI dose decreased or discontinued because of adverse effects. CONCLUSIONS AND CLINICAL IMPORTANCE: Twice daily dose frequency might optimize the cardioprotective benefit of ACEIs.

Benazepril hydrochloride protects against doxorubicin cardiotoxicity by regulating the PI3K/Akt pathway.

Doxorubicin (DOX) stimulates the generation of reactive oxygen species, thereby impairing mitochondrial functions. Angiotensin-converting enzyme inhibitors (ACEIs) have been identified to exhibit protective effects on cardiovascular diseases. The present study aimed to test the hypothesis that an ACEI benazepril hydrochloride (HCl) may protect against DOX-induced cardiotoxicity. The DOX injury model was established using rat embryonic cardiac myoblast cells (H9c2 cell line) treated with DOX in vitro. H9c2 cells were treated with benazepril-HCl, DOX or a mixture of DOX and benazepril-HCl to measure the activities of myocardial enzymes including lactate dehydrogenase (LDH), superoxide dismutase, catalase and glutathione peroxidase, in addition to the concentration of malondialdehyde in the culture medium. Cells without any treatment were used as a control. DOX treatment increased the levels of activity of myocardial enzymes in H9c2 cells compared with those in the untreated control cells. Additionally, co-treatment with benazepril-HCl significantly reduced the levels of apoptosis occurring due to DOX-mediated cellular damage. The mechanistic experiment revealed that pretreatment with benazepril-HCl counteracted the DOX-induced oxidative stress and suppressed the activation of apoptosis via the PI3K/Akt signaling pathway. By contrast, an Akt inhibitor (MK2206) inhibited the protective effects of benazepril-HCl against DOX-induced H9c2 cell injury, as revealed by increased LDH release in H9c2 cells. These results suggested that benazepril-HCl may potentially be administered as an adjuvant for DOX in long-term clinical use.

A sensitive and efficient LC-MS/MS method for the bioanalysis of fosinopril diacid from human plasma and its application for a bioequivalence study in humans.

Fosinopril diacid is an angiotensin converting enzyme inhibitor with efficient antihypertensive action. It is an active metabolic product formed in the body from hydrolysis of its prodrug Fosinopril. A sensitive, rapid method with high recovery for Fosinopril diacid from human plasma was developed. Solid-phase extraction technique employing Waters Oasis SPE cartridges gave clean samples with very high recovery of 97%. The analyte along with its internal standard (Benazepril hydrochloride) were chromatographed on an XTerra RP8 column (4.6 × 50 mm, 5 µm) using methanol-ammonium acetate buffer (10 mm; 90:10, v/v) as the mobile phase. A triple quadrupole mass spectrometer equipped with electrospray ionization source operated in the negative ion mode was used for detection. Multiple reaction monitoring scan mode was used for monitoring the transitions from m/z 434.00 → 237.15 for Fosinopril diacid and m/z 423.10 → 174.00 for Benazepril hydrochloride. Beer-Lambert's law was obeyed in the range of 0.50-1,500.00 ng/ml (r = 0.9993). The stability of the drugs in human plasma and in stock solution was proved by performing stability tests as per US Food and Drug Administration guidelines. The method was successfully applied for a bioequivalence study of Fosinopril diacid in 36 healthy, adult, male volunteers under fasting conditions.

Changes in systolic blood pressure in dogs with pituitary dependent hyperadrenocorticism during the first year of trilostane treatment.

BACKGROUND: Systemic hypertension (SH) is common in dogs and humans with hypercortisolism and can persist after treatment. OBJECTIVES: To evaluate changes in prevalence of SH and systolic blood pressure (SBP) in dogs with pituitary-dependent hyperadrenocorticism (PDH) during the first year of trilostane treatment, its relationship with disease control and selected laboratory variables, and their response to antihypertensive treatment. ANIMALS: Fifty-one dogs with PDH treated with trilostane Q12h. METHODS: Prospective case series study. Dogs were evaluated at diagnosis (T0) and 1, 3, 6, and 12 months (T12). Dogs were classified as nonhypertensive (SBP < 160 mm Hg) or hypertensive (SBP≥160 mm Hg) and subclassified according to target organ damage (TOD) risk. Hypertensive dogs were treated with benazepril and, if control of SH was not achieved, amlodipine was added. RESULTS: Prevalence of SH decreased from T0 (36/51) to T12 (17/37; P = .01). Changes in SBP during the study were influenced by the risk of TOD at T0. In severely hypertensive (SBP ≥ 180 mm Hg) dogs, the decrease in SBP was more pronounced whereas in normotensive (SBP < 140 mm Hg) dogs SBP increased slightly (P = .00). Blood pressure was not associated with disease control. Antihypertensive treatment was needed in 31/51 dogs, and in 13/31 dogs additional SH control with amlodipine was required. One third of nonhypertensive dogs at T0 required treatment with benazepril because SH developed during follow-up. CONCLUSIONS AND CLINICAL IMPORTANCE: In dogs with PDH, SBP should be measured at every visit, regardless of disease control or SBP at diagnosis. More than 1 drug may be necessary to manage SH in affected dogs.

Fabrication of pH-sensitive graphene oxide-Benazepril carrier as biosafety controlled release systems.

A novel graphene oxide (GO)-based carrier was fabricated for the controlled release of Benazepril (BENA). Freeze dried samples of GO-BENA carrier were prepared for controlled drug release at different pHs (pH = 2, 7, and 10) and release kinetics indicate BENA desorption from GO is by Fickian diffusion. The BENA yield from the carrier amounted to ~55% of the adsorbed material in a strongly acidic medium after 50 h. Binding fractions of BENA to 10 mg/L GO was determined for different solution concentrations of the drug. In vitro assays of cell proliferation (WST-1 kit), cell structural integrity (LDH kit) and flow cytometric indicators of necrosis in three different cell lines (CACO-2, SGC-7901, and primary mouse hepatic fibroblast) all demonstrated that the GO carrier had a good biocompatibility. The pH-dependent release sensitivity of the GO-based carrier suggests that it is a potential candidate for use in the controlled release of drugs in the acidic environment of the stomach.

Protective effects of irbesartan and benazepril against vaginal vascular remodeling and fibrosis in female spontaneously hypertensive rats.

OBJECTIVE: To compare the potential beneficial effects of the angiotensin converting enzyme inhibitor (ACEI) benazepril and the angiotensin II receptor 1 blocker (ARB) irbesartan on vaginal vascular remodeling and fibrosis in female spontaneously hypertensive rats (SHRs). METHODS: Twelve-week-old female SHRs were treated with irbesartan or benazepril for 12 weeks. Vaginal renin angiotensin system (RAS) components were detected by polymerase chain reaction and western blot and vaginal α-smooth muscle actin (α-SMA), endothelial nitric oxide synthase (eNOS), and collagen III (Col III) were analyzed by western blot. Vaginal tissue sections were examined by hematoxylin and eosin staining, Masson trichrome staining, and immunohistochemical analysis of α-SMA and Col III. RESULTS: Irbesartan and benazepril had different impacts on vaginal RAS components. Both agents decreased vaginal α-SMA and Col III and increased eNOS expression in SHR. The wall/lumen thickness ratio of vaginal arterioles was similarly decreased following irbesartan and benazepril treatment. Both drugs also decreased collagen deposition in SHRs. There was no difference in vaginal vascular remodeling or fibrosis between the two groups. CONCLUSIONS: Irbesartan and benazepril have different effects on vaginal RAS expression but similar positive effects against vaginal vascular remodeling and fibrosis.

Postnatal renin-angiotensin system inhibition prevents renal damage from prenatal inflammation in rats.

OBJECTIVE: To assess the protective role of benazepril, an angiotensin-converting enzyme inhibitor, in renal damage caused by prenatal inflammation. METHODS: Saline or lipopolysaccharide were administered intraperitoneally to pregnant Sprague- Dawley rats on gestation days 8, 10, and 12. After birth, offspring received either tap water or benazepril in water between 7 and 68 weeks. Blood pressure, blood urea nitrogen, creatinine, and 24-h urine volume were measured as indices of renal function. Hematoxylin, eosin, periodic acid-Schiff, and Sirius Red staining were used to evaluate renal damage. RESULTS: Postnatal benazepril treatment ameliorated hypertension and restored normal 24-h urine volume and blood urea nitrogen and serum creatinine levels. Benazepril treatment also reduced glycoprotein accumulation and fibrosis in the glomerulus and in tubular epithelial cells and inhibited nuclear factor-kappa B activation. CONCLUSION: Together with our previous findings that postnatal inhibition of nuclear factor-kappa B activation blocks intra-renal renin-angiotensin system activation, our current data demonstrate that intra-renal activation of the renin-angiotensin system interacts with nuclear factor-kappa B activation to cause renal damage in adulthood following prenatal inflammation.

[Effect of benazepril on nuclear factor E2 related factor 2, nicotinamide adenine dinucleotide phosphate oxidase and reactive oxygen species in rats with hepatic fibrosis].

Objective: To study the effect of benazepril on the expression of nuclear factor E2 related factor 2 (Nrf2), nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) and reactive oxygen species (ROS) concentration in rats with hepatic fibrosis and to explore the possible antifibrotic mechanism of benazepril. Methods: Twenty-two healthy male Sprague-Dawley rats were randomly divided into 3 groups: control group (6 rats), model group (8 rats) and benazepril treatment group (8 rats). Two rats died during modeling and treatment in the model group and the benazepril treatment group, and a model of hepatic fibrosis induced by carbon tetrachloride (CCL(4)) was established. The rats in benazepril group were given benazepril for 8 weeks by gastric gavage. The assessment of liver tissue damage in each group was measured using conventional hematoxylin-eosin and Masson staining. The mRNA level of Nrf2, NOX4 in liver tissue was detected by RT-PCR, and serum ROS concentration was determined by colorimetry. All data were expressed in mean ± standard deviations, and were analyzed using SPSS21.0 statistical software. The data were compared using one-way analysis of variance, and the LSD-t method was used for pairwise comparison between the two groups. The correlation analysis was performed by Spearman's correlation analysis. Results: In the liver of the model group, with the aggravation of liver fibrosis the expression of Nrf2mRNA, NOX4 mRNA and ROS concentration were higher than control group [(4.01 ± 3.40), (31.78 ± 3.96), (1.82 ± 0.46) µg/ ml vs. (0.12 ± 0.11), (2.03 ± 0.31), (1.56±0.84) µg/ml, P < 0.05]. After benazepril treatment, NOX4 mRNA expression and ROS concentration were decreased than the model group [(15.93 ± 5.01), (0.78 ± 0.44) µg/ml vs. (31.78 ± 3.96), (1.82 ± 0.46) µg /ml, P < 0.05], while Nrf2 mRNA expression was higher than the model group [(6.69 ± 4.86) vs. (4.01 ± 3.40), P < 0.05]. There was a positive correlation between Nrf2 and NOX4, Nrf2 and ROS, and NOX4 and ROS (r = 0.616, 0.411, 0.802, P < 0.05). Conclusion: Benazepril may exert an anti-hepatic fibrosis effect by activating Nrf2 expression, or may inhibit the ROS-mediated oxidative stress in response to NOX4.

Combination of leflunomide and benazepril reduces renal injury of diabetic nephropathy rats and inhibits high-glucose induced cell apoptosis through regulation of NF-κB, TGF-ß and TRPC6.

Objective: To investigate effects of combination use of leflunomide and benazepril on diabetic nephropathy (DN) both in vivo and in vitro. Methods: The streptozotocin (STZ) induced Sprague-Dawley rats were treated with leflunomide (15 mg/kg/d), benazepril (15 mg/kg/d) or both the two drugs. Fasting blood glucose (FBG) and renal function indexes including blood urea nitrogen (BUN), serum creatinine (Scr), and proteinuria and kidney/body weight ratio (KW/BW) were measured. HE staining was used for histological analysis. The rat glomerular mesangial cells (RMCs) were treated with high-glucose (150 mg/ml) and the leflunomide and benazepril with both concentrations of 50 µmol/l were used to treat the high-glucose induced cells. TUNEL assay was used for measurement of cell apoptosis. Western blotting was conducted to determine expression of nuclear factor Kappa B (NF-κB), transforming growth factor-ß (TGF-ß) and transient receptor potential canonical 6 (TRPC6). Results: The body weight was significantly lower and all indexes of FBG, BUN, Scr, proteinuria and KW/BW ratio, GFR, as well as inflammatory factors TNF-α and IL-6 were significantly increased in the DN group after STZ treatment for 4 weeks. The treatment with leflunomide, benazepril or the both dramatically reduced the above effects induced by STZ, and the alteration was the most significant in the combination group. Treatment of leflunomide and benazepril significantly reduced expression levels of NF-κB, TGF-ß and TRPC6 in renal tissues of DN rats as well as in high-glucose induced RMCs. It was also observed leflunomide and benazepril reduced high-glucose induced cell apoptosis of RMCs. Conclusion: The combination use of leflunomide and benazepril could improve the renal function and reduce the renal injury of DN rats and could reduce the levels of NF-κb, TGF-ß and TRPC6 in both DN rats and high-glucose induced RMCs.

Multi-spectroscopic approaches and molecular simulation research of the intermolecular interaction between the angiotensin-converting enzyme inhibitor (ACE inhibitor) benazepril and bovine serum albumin (BSA).

Benazepril, a common ACE inhibitor, widely used in the treatment of arterial hypertension and congestive heart failure. In this study, We evaluated the characteristics of the interaction between benazepril and BSA under the simulated physiological condition (pH7.4) through various spectroscopic and molecular docking methods. Fluorescence and absorption spectroscopy results showed benazepril quenched the intrinsic fluorescence of BSA through a combined dynamic and static quenching mechanism. The number of binding sites (n) and the binding constant (Kb) of benazepril-BSA complex were circa 1 and 6.81×103M-1 at 298K, respectively, indicating that the binding affinity between benazepril and BSA was moderate. The displacement experiments confirmed that benazepril binding to the site I of BSA, which was quite in accordance with molecular docking. The values of the Gibbs free energy (ΔG0), enthalpic change (ΔH0) and entropic change (ΔS0) were negative, verifying that van der Waals force and hydrogen bonding interaction played a predominant roles in the process of spontaneous bonding. Furthermore, a slight change of the conformation in BSA upon benazepril interaction was proved through SF, 3-DF and FTIR spectroscopy results.

Effect of benazepril on nuclear factor E2 related factor 2, nicotinamide adenine dinucleotide phosphate oxidase and reactive oxygen species in rats with hepatic fibrosis / 中华肝脏病杂志

Objective@#To study the effect of benazepril on the expression of nuclear factor E2 related factor 2 (Nrf2), nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) and reactive oxygen species (ROS) concentration in rats with hepatic fibrosis and to explore the possible antifibrotic mechanism of benazepril.@*Methods@#Twenty-two healthy male Sprague-Dawley rats were randomly divided into 3 groups: control group (6 rats), model group (8 rats) and benazepril treatment group (8 rats). Two rats died during modeling and treatment in the model group and the benazepril treatment group, and a model of hepatic fibrosis induced by carbon tetrachloride (CCL4) was established. The rats in benazepril group were given benazepril for 8 weeks by gastric gavage. The assessment of liver tissue damage in each group was measured using conventional hematoxylin-eosin and Masson staining. The mRNA level of Nrf2, NOX4 in liver tissue was detected by RT-PCR, and serum ROS concentration was determined by colorimetry. All data were expressed in mean ± standard deviations, and were analyzed using SPSS21.0 statistical software. The data were compared using one-way analysis of variance, and the LSD-t method was used for pairwise comparison between the two groups. The correlation analysis was performed by Spearman’s correlation analysis.@*Results@#In the liver of the model group, with the aggravation of liver fibrosis the expression of Nrf2mRNA, NOX4 mRNA and ROS concentration were higher than control group [(4.01 ± 3.40), (31.78 ± 3.96), (1.82 ± 0.46) μg/ ml vs. (0.12 ± 0.11), (2.03 ± 0.31), (1.56±0.84) μg/ml, P < 0.05]. After benazepril treatment, NOX4 mRNA expression and ROS concentration were decreased than the model group [(15.93 ± 5.01), (0.78 ± 0.44) μg/ml vs. (31.78 ± 3.96), (1.82 ± 0.46) μg /ml, P < 0.05], while Nrf2 mRNA expression was higher than the model group [(6.69 ± 4.86) vs. (4.01 ± 3.40), P < 0.05]. There was a positive correlation between Nrf2 and NOX4, Nrf2 and ROS, and NOX4 and ROS (r = 0.616, 0.411, 0.802, P < 0.05).@*Conclusion@#Benazepril may exert an anti-hepatic fibrosis effect by activating Nrf2 expression, or may inhibit the ROS-mediated oxidative stress in response to NOX4.

Influence of bisoprolol combined benazepril on ECG and left ventricular diastolic function in hyperten‐sive patients with acute heart failure／ / 心血管康复医学杂志

To explore influence of bisoprolol combined benazepril on ECG and left ventricular diastolic function in hypertensive patients with acute heart failure (AHF).Methods :A total of 124 hypertensive patients with AHF were randomly and equally divided into routine treatment group and combined treatment group (received biso‐prolol combined benazepril based on routine treatment ) ,both groups were treated for two months .Therapeutic effect ,ECG indexes ,left ventricular diastolic function indexes ,levels of heart failure and myocardial injury markers etc .before and after treatment were compared between two groups .Results : After two‐month treatment ,total ef‐fective rate of combined treatment group was significantly higher than that of routine treatment group (96. 77% vs. 82. 26%, P＝0.008) ;compared with routine treatment group ,there were significant reductions in QRS wave dura‐tion [ (103. 87 ± 9.70) ms vs.(94.12 ± 8. 93) ms] ,QTc duration [ (432.37 ± 33. 24) msvs .(418.96 ± 29. 64) ms] , plane QRS‐T angle [ (59.75 ± 26. 61)°vs.(48.19 ± 22.30)°] ,mitral annulus late diastolic peak flow velocity (Am) [ (12.84 ± 3.40) cm／svs .(11. 39 ± 3. 11) cm／s] ,plasma levels of N terminal pro brain natriuretic peptide [ (1. 20 ± 0.58) μg／L vs .(0. 75 ± 0.47) μg／L] ,carbohydrate antigen 125 [ (19.10 ± 9.24) U／ml vs.(13.93 ± 7.85) U／ml] ,galectin‐3 [ (4.72 ± 2. 25) μg／L vs .(3.28 ± 1. 65) μg／L] ,cardiac troponin I [ (1.93 ± 0. 97) μg／L vs.(1. 46 ± 0. 85) μg／L] ,and significant rise in mitral early／late diastolic peak flow velocity (E／A) [(1. 18 ± 0.30) vs.(1. 31 ± 0. 28)] and mitral annulus early diastolic peak flow velocity (Em) [ (12.90 ± 3. 76) cm／svs.(14. 49 ± 3.25) cm／s] in combined treatment group , P＜0. 05 or ＜0.01. There was no significant difference in incidence rates of ad‐verse reactions between two groups , P＞0.05 all.Conclusion :Bisoprolol combined benazepril possesses significant therapeutic effect on hypertensive patients with AHF ,and its improving effect on ECG indexes and left ventricular diastolic function is significant .

Influence of rifampin in effectiveness of antihypertensive drugs in patients with hypertension: A case report and literature review / 吉林大学学报(医学版)

Objective: To discuss the diagnosis and treatment process of abnormally elevated blood pressure in the patient treated with rifampicin and antihypertensive drugs, to analyze the interaction between rifampicin and antihypertensive drugs, and to improve the clinicians' understanding of the administration in the patients. Methods: The clinical materials of a patient treated with rifampicin and antihypertensive drugs were collected, and the relationship between the blood pressure change and drug was analyzed. The changes of concentrations of dihydropyridine-based calcium antagonists after administration of rifampin were observed and the relative literatures were reviewed. Results: A 58-year-old man with coughing and coughing for 1 month was admitted to hospital. The patient was definitely diagnosed as tuberculosis and hypertension before admission; the patient was treated with rifampicin, isoniazid, ethambutol, pyrazinamide, and felodipine together. The original treatment plan was continued and the blood pressure of the patient was monitored. On the 9th day of anti-tuberculosis treatment, the patient developed dizziness, chest tightness, and severe fluctuations in blood pressure. Then rifampicin was stopped and antihypertensive drugs were adjusted. At the beginning of blood pressure fluctuation of the patient, the combination of angiotensin-converting enzyme inhibitors and the increasing dose of dihydropyridine-based calcium antagonists did not control the blood pressure. The blood pressure began to decrease significantly at 36 h after rifampin was stopped. On the 18th day of anti-tuberculosis treatment, the original antihypertensive plan was restored and the blood pressure remained stable. Conclusion: Rifampicin can sometimes significantly reduce the effect iveness of antihypertensive drugs (such as dihydropyridine calcium antagonists), and the clinicians should pay attention to it.