Combination Of Angiotensin-converting Enzyme Inhibitor Research Articles

Angiotensin-converting enzyme inhibitors have adverse effects in anti-angiogenesis therapy for hepatocellular carcinoma.

At present, anti-angiogenic drugs (AADs) are widely used in the systemic treatment of hepatocellular carcinoma (HCC) or other types of cancer, and have achieved good anti-cancer effect, whereas treatment-related proteinuria can affect the routine use of AADs, which in turn abates the overall efficacy. Currently, most clinicians prescribe angiotensin-converting enzyme inhibitors (ACEIs) to alleviate proteinuria according to diabetic nephropathy guidelines or expert recommendations. However, the efficacy of ACEIs in reducing AAD-related proteinuria and its effect on the anticancer effect of AADs is unknown. Our clinical data showed that some HCC patients experienced tumor progression by ACEIs administration for the treatment of proteinuria caused by AADs. Here, we confirmed that in different tumor-bearing mouse models, ACEIs did not delay the appearance of proteinuria or alleviate proteinuria caused by AADs but compromised the anticancer efficacy of AADs. This effect is unrelated to the change in the VEGF signaling pathway. Our data showed that the combination of ACEIs and AADs flared the production of kidney-derived erythropoietin (EPO). In turn, EPO compromises the anti-angiogenic effects of AADs and decreases antitumor activity. In conclusion, for the treatment of proteinuria caused by AADs, ACEIs have no efficacy while also promoting AADs resistance. This finding is of great significance to guide clinical standardized management of side effects of anti-angiogenic therapy for cancer patients.

SITUATION OF USING DRUGS FOR TREATMENT HYPERTENSION OF PATIENTS WITH RENAL FAILURE STAGE IV

Objective: To investigate the use of drugs in prescribing for treatment of hypertension in patients with stage IV chronic renal failure at An Sinh General Hospital. Objects and methods: study of retrospective,cross-sectional description of 153 medical records of patients diagnosed with hypertension with stage IV chronic renal failure who were treated in the Department of Endocrinology - Dialysis of An Sinh General Hospital, Ho Chi Minh City, from June 1 st , 2019 to May 31 st , 2020. Results: ACE inhibitors and calcium inhibitors were the two most commonly used groups of drugs. The adrenergic blocker group and the diuretic group were used less common, the Angiotensin receptor inhibitors (ARI) used the least. 75.82% of patients must use the combination regimen; in which the combination regimen of 2 drugs and 3 drugs was used the most. The most common combination pair seen in the sample in a two-drug combination regimen were ACE inhibitors and diuretics, followed by ACE inhibitors and calcium inhibitors. With a combination of 3 drug groups, the most common combination was ACE inhibitors, calcium inhibitors and adrenergic inhibitors. Conclusion: ACE inhibitors and calcium channel blockers were mainly used. Combination regimen of 2 and 3 drugs accounted for a high proportion, in which the combination of ACE inhibitors with diuretics and ACE inhibitors with calcium channel blockers and adrenergic inhibitors were mainly used.

Angiotensin-Converting Enzyme Inhibitors Have Adverse Effects in Anti-Angiogenesis Therapy for Hepatocellular Carcinoma

Background: Currently, most clinicians prescribe angiotensin-converting enzyme inhibitors (ACEIs) to alleviate proteinuria caused by anti-angiogenic drugs (AADs) according to diabetic nephropathy guidelines or expert recommendations. However, the efficacy ACEIs and potential cancer promoting effect are controversial. This study aimed at confirming whether ACEIs are beneficial in anti-angiogenesis therapy for hepatocellular carcinoma. Methods: In clinic, we observed the impact of ACEIs on AADs during the treatment of hepatocellular carcinoma. Next, we established different tumor-bearing mouse models to confirm that whether ACEIs have any effect on the anti-cancer efficacy and proteinuria side effects of AADs. Further, we confirmed the relevant mechanism in vivo. Findings: Our clinical data have shown that some hepatocellular carcinoma (HCC) patients experienced tumor progression by ACEIs administration for the treatment of hypertension or proteinuria caused by AADs. We have confirmed that in different tumor-bearing mouse models, ACEIs did not delay the appearance of proteinuria or alleviate proteinuria caused by AADs but compromised the anticancer efficacy of AADs. This effect is unrelated to a change in the VEGF signaling pathway. Our data showed that the combination of ACEIs and AADs flared the production of kidney-derived erythropoietin (EPO). In turn, EPO compromises the anti-angiogenic effects of AADs and decreases antitumor activity. Interpretation: For the treatment of proteinuria caused by AADs, ACEIs have no efficacy but promote drug resistance. Kidney-derived EPO is mainly responsible for ACEIs induced anti-angiogenesis resistance. Funding Statement: This study was supported by the National Natural Science Foundation of China (No. 81672884) and the National Science and Technology Major Project of China (No. 2017ZX10203207-004-005). Declaration of Interests: The authors have declared that no conflict of interest exists. Ethics Approval Statement: All human studies were approved by the Clinical Research Ethics Committee of Tianjin Medical University Cancer Institute. All animal experiments were carried out in accordance with a protocol approved by the ethics committee of the Institutional Animal Care of Tianjin Medical University Cancer Institute and Hospital.

Effect of a combination of angiotensin-converting enzyme inhibitor and diuretic on the frequency and parameters of lower limb venous reflux in working-age men with hypertension

Aim. To study the effect of combined antihypertensive therapy on the characteristics of venous reflux in working-age men with hypertension (HTN).Material and methods. We examined 44 men aged 30-50 years with uncontrolled HTN. The dynamics of the rate, temporal and velocity parameters of venous reflux was analyzed for a 14-15 days of combined therapy with an angiotensin-converting enzyme inhibitor (perindopril, 8 mg) and a diuretic (indapamide, 1,5 mg) both in the general group (n=44) and in groups of 22 men with/without chronic venous disease (CVD). CVD was diagnosed by physical examination according to the CEAP criteria. Reflux was assessed at rest by ultrasound of symmetric superficial, deep and perforator veins.Results. In the general group of patients (n=44), a decrease in blood pressure was associated with significant negative dynamics of the reflux rate in all veins from 0 to 37, a positive dynamics only from 7 to 0 (p=0,0001). Analysis of the dynamics of reflux duration and velocity before and after treatment did not show any differences. The use of combination therapy in patients with HTN and CVD was associated with an increase in the reflux number (p=0,0001), while in patients with HTN without CVD, no significant dynamics was recorded. The proportion of patients with reflux after treatment in the CVD group more than doubled. Comparison of the temporal and velocity reflux parameters after treatment between the groups with/without CVD did not reveal any differences.Conclusion. Two-week therapy with an angiotensin-converting enzyme inhibitor and a diuretic in working-age men with uncontrolled hypertension is accompanied by the appearance of a significant number of new venous refluxes, which is due to the presence of CVD among patients with hypertension. After treatment, the proportion of patients with reflux in the group with AH and CVD more than doubled.

Efficacy and Safety of Renin-Angiotensin Aldosterone System Inhibitor in Patients with IgA Nephropathy: A Meta-Analysis of Randomized Controlled Trials

Angiotensin converting enzyme inhibitor (ACEI) and angiotensin receptor blocker (ARB) as the commonly used renin-angiotensin aldosterone system inhibitor are widely used in patients with IgA nephropathy (IgAN), but the effect is controversy. In this study, we used a meta-analysis to evaluate the efficacy and safety of ACEI and/or ARB for the patients with IgAN. Two investigators independently searched the PubMed, EMBASE, the Cochrane Library, EBSCO, and Wiley databases without language restrictions. We collected the clinical randomized controlled trials (RCTs) on "ACEI and/or ARB for the patients with IgAN" published before December 31, 2018, and performed data extraction and quality analysis on the included studies, and analyzed data using RevMan 5.2 software. A total of 10 RCTs (635 patients) were included in our analysis. Alone use of ACEI (MD=-0.75, 95%CI: -1.28-0.21, P=0.006) or ARB (MD=-0.56, 95%CI: -0.82-0.30, P< 0.001) or a combination of ACEI and ARB (MD=-0.63, 95%CI: -0.87-0.38, P<0.001) significantly reduced the levels of proteinuria in patients with IgAN. However, whether using ACEI or ARB alone or in combination with ACEI and ARB, there was no significant effect on serum creatinine, 24-creatinine clearance and glomerular filtration rate in patients with IgAN. The use of ACEI and ARB significantly reduces the levels of proteinuria in patients with IgAN, but more large-sample RCTs with long-term follow-up are needed for confirming our results and guiding clinical treatment.

The effects of the combination of angiotensin-converting enzyme inhibitor and diuretic on the lower limb venous circulation in men with hypertension and chronic venous disorders

Aim. To study the effects of angiotensin converting enzyme (ACE) inhibitor and diuretic combination on the lower limb venous circulation in men with hypertension (HTN) and chronic venous disorders (CVD).Material and methods. The study included 37 men with uncontrolled hypertension at the age of 46 (40-49) years, which were divided into two groups: 20 patients with objective signs of CVD (CEAP criteria) and 17 patients without CVD. During hospitalization, all participants received antihypertensive therapy with a combination of ACE inhibitor and diuretic. Vein Doppler ultrasound at rest was performed on the day of hospitalization and after 14 days. The diameter and the area of vein lumen, flow velocity and peripheral venous pressure (PVP) were recorded. Mann-Whitney and Wilcoxon tests were used for statistical analysis.Results. Initially, patients with CVD had higher values of PBP (by 26%), diameter and area of the vein lumen (53%) and flow velocity (by 14%) than in patients without CVD. As a result of therapy, in the group of patients with HTN and without CVD, systolic (SBP) and diastolic blood pressure (DBP) decreased to the target levels, PVP decreased by 13%, vein diameter increased by 27%, blood flow velocity decreased by 15%. Therapy in patients with CVD led to the normalization of SBP, DBP, and a decrease in PVP and flow velocity by 31% and 33%, respectively. No significant changes in the diameter and cross-sectional area of lower limb veins were noted.Conclusion. The obtained data showed that 14-day antihypertensive therapy with ACE inhibitor and diuretic in patients with HTN and CVD, unlike patients with HTN and without CVD, did not led to vein dilation, but was associated with flow velocity and PVP decrease. By therapy’s end, most of venous hemodynamic parameters, including PVP, were identical in the studied groups.

Beneficial association of angiotensin-converting enzyme inhibitors and statins on the occurrence of possible Alzheimer\u2019s disease after traumatic brain injury

BackgroundPathological analysis of brain tissue from animals and humans with a history of traumatic brain injury (TBI) suggests that TBI could be one of the risk factors facilitating onset of dementia with possible Alzheimer’s disease (AD), but medications to prevent or delay AD onset are not yet available.MethodsThis study explores four medication classes (angiotensin-converting enzyme inhibitors (ACEI), beta blockers, metformin, and statins) approved by the Food and Drug Administration (FDA) for other indications and evaluates their influence when used in combination on the risk of possible AD development for patients with a history of TBI. We identified patients with history of TBI from an existing Department of Veterans Affairs (VA) national database. Among 1,660,151 veterans who used VA services between the ages of 50 to 89 years old, we analyzed 733,920 patients, including 15,450 patients with a history of TBI and 718,470 non-TBI patients. The TBI patients were followed for up to 18.5 years, with an average of 7.7 ± 4.7 years, and onset of dementia with possible AD was recorded based on International Statistical Classification of Diseases (ICD) 9 or 10 codes. The effect of TBI on possible AD development was evaluated by multivariable logistic regression models adjusted by age, gender, race, and other comorbidities. The association of ACEI, beta blockers, metformin, statins, and combinations of these agents over time from the first occurrence of TBI to possible AD onset was assessed using Cox proportional hazard models adjusted for demographics and comorbidities.ResultsVeterans with at least two TBI occurrences by claims data were 25% (odds ratio (OR) = 1.25, 95% confidence intervals (CI) (1.13, 1.37)) more likely to develop dementia with possible AD, compared to those with no record of TBI. In multivariable logistic regression models (propensity score weighted or adjusted), veterans taking a combination of ACEI and statins had reduced risk in developing possible AD after suffering TBI, and use of this medication class combination was associated with a longer period between TBI occurring and dementia with possible AD onset, compared to patients who took statins alone or did not take any of the four target drugs after TBI.ConclusionsThe combination of ACEI and statins significantly lowered the risk of development of dementia with possible AD in a national cohort of people with a history of TBI, thus supporting a clinical approach to lowering the risk of dementia with possible AD.

The association of long-term outcome and biological sex in patients with acute heart failure from different geographic regions.

Recent data from national registries suggest that acute heart failure (AHF) outcomes might vary in men and women, however, it is not known whether this observation is universal. The aim of this study was to evaluate the association of biological sex and 1-year all-cause mortality in patients with AHF in various regions of the world. We analysed several AHF cohorts including GREAT registry (22 523 patients, mostly from Europe and Asia) and OPTIMIZE-HF (26 376 patients from the USA). Clinical characteristics and medication use at discharge were collected. Hazard ratios (HRs) for 1-year mortality according to biological sex were calculated using a Cox proportional hazards regression model with adjustment for baseline characteristics (e.g. age, comorbidities, clinical and laboratory parameters at admission, left ventricular ejection fraction). In the GREAT registry, women had a lower risk of death in the year following AHF [HR 0.86 (0.79-0.94), P < 0.001 after adjustment]. This was mostly driven by northeast Asia [n = 9135, HR 0.76 (0.67-0.87), P < 0.001], while no significant differences were seen in other countries. In the OPTIMIZE-HF registry, women also had a lower risk of 1-year death [HR 0.93 (0.89-0.97), P < 0.001]. In the GREAT registry, women were less often prescribed with a combination of angiotensin-converting enzyme inhibitors and beta-blockers at discharge (50% vs. 57%, P = 0.001). Globally women with AHF have a lower 1-year mortality and less evidenced-based treatment than men. Differences among countries need further investigation. Our findings merit consideration when designing future global clinical trials in AHF.

Combined Effects of Eicosapentaenoic Acid and Adipocyte Renin-Angiotensin System Inhibition on Breast Cancer Cell Inflammation and Migration.

Obesity is a major risk factor for breast cancer (BC). Obesity-related metabolic alterations such as inflammation and overactivation of the adipose renin–angiotensin system (RAS) may contribute to the progression of BC. Clinically used antihypertensive drugs such as angiotensin-converting enzyme inhibitors (ACE-I) and dietary bioactive components such as eicosapentaenoic acid (EPA) are known for their anti-inflammatory and adipose RAS blocking properties. However, whether EPA enhances the protective effects of ACE-I in lessening adipocyte inflammation on BC cells has not been studied. We hypothesized that combined EPA and ACE-I would attenuate BC cell inflammation and migration possibly via adipose RAS inhibition. To test our hypothesis, we examined the (i) direct effects of an ACE-I (captopril (CAP)) or EPA, individually and combined, on MCF-7 and MDA-MB-231 human BC cells, and the (ii) effects of conditioned medium (CM) from human adipocytes pretreated with the abovementioned agents on BC cells. We demonstrated that CM from adipocytes pretreated with EPA with or without captopril (but not direct treatments of BC cells) significantly reduced proinflammatory cytokines expression in both BC cell lines. Additionally, cell migration was reduced in MDA-MB-231 cells in response to both direct and CM-mediated CAP and/or EPA treatments. In summary, our study provides a significant insight into added benefits of combining anti-inflammatory EPA and antihypertensive ACE-I to attenuate the effects of adipocytes on breast cancer cell migration and inflammation.

Effect of Combination ACEI (Angiotensin Converting Enzyme Inhibitor) and Diuretics on Potassium Levels of Congestive Heart Failure Patients

ACEI (Angiotensin Converting Enzyme Inhibitors) and diuretics are now the treatment options for heart failure patients. However, the use of ACEI and diuretics can cause potassium balance disorders. This study aimed to evaluate the use of ACEI and diuretics combinations on potassium levels in patients with congestive heart failure. This study used analytical research and sampling, done in total sampling. Samples were divided into 2 groups, group with combination of ACEI, furosemide and spironolactone along with combination group of ACEI and furosemide. Total samples obtained were 38 patients. The results showed that the averaged potassium levels in combinations of ACEI, furosemide and spironolactone before treatment were 3.95mmol/L and after treatment were 3.85 mmol/L (p = 0.061), the averaged potassium levels before receiving therapy were 4.20 mmol/L and after receiving 4.14 mmol/L therapy (p = 0.070) in combinations of ACEI and furosemide. In combinations of ACEI, furosemide and spironolactone, of a total of 25 patients, hypokalemia was found in 6 patients (24%), normal in 19 patients (76%) and 0 patient had hyperkalemia (0%), while combinations of ACEI and furosemide, of a total of 13 patients, all patients have normal potassium levels. So it can be concluded that there were no significant changes between potassium levels before and after receiving therapy of ACEI and diuretics combination.

ACE2 as a potential therapeutic target for pandemic COVID-19.

SARS-CoV-2 virus invades the host through angiotensin-converting enzyme 2 (ACE2) receptors by decreasing the ACE2 expression of the host. This disturbs the dynamic equilibrium between the ACE/Ang II/AT1R axis and ACE2/Ang (1–7)/Mas receptor axis. Therefore, the clinically approved drugs belonging to (i) angiotensin converting enzyme (ACE) inhibitors such as captopril, and enalaprilat, (ii) angiotensin-receptor blockers (ARBs) such as losartan, candesartan, olmesartan, azilsartan, irbesartan, and telmisartan and (iii) the combination of ACE inhibitors and ARBs such as losartan with lisinopril and captopril with losartan, and (iv) recombinant ACE2, were studied for their ability to activate ACE2 in different medical conditions including hypertension, inflammation, cardiovascular, renal and lung diseases. These clinically approved drugs were found to activate ACE2 that had been downregulated in different medical conditions including hypertension, inflammation, cardiovascular, renal and lung diseases. Therefore, these drugs may be repurposed to re-activate the downregulated ACE2 of COVID-19 patients. These drugs either alone or in combination may be repurposed as prophylactics and therapeutics against SARS-CoV-2 virus.

Влияние комбинации ингибитора ангиотензинпревращающего фермента и блокатора кальциевых каналов на венозную гемодинамику нижних конечностей при коморбидности артериальной гипертензии и хронических заболеваний вен

Влияние комбинации ингибитора ангиотензинпревращающего фермента и блокатора кальциевых каналов на венозную гемодинамику нижних конечностей при коморбидности артериальной гипертензии и хронических заболеваний вен

Combined inhibition of CCR2 and ACE provides added protection against progression of diabetic nephropathy in Nos3-deficient mice.

Macrophage-mediated renal injury promotes the development of diabetic nephropathy. Blockade of chemokine (C-C motif) receptor 2 (CCR2) inhibits kidney macrophage accumulation and early glomerular damage in diabetic animals. This study tested early and late interventions with a CCR2 antagonist (CCR2A) in a model of progressive diabetic glomerulosclerosis and determined whether CCR2A provides added benefit over conventional treatment with an angiotensin-converting enzyme inhibitor (ACEi). Diabetes was induced in hypertensive endothelial nitric oxide synthase (Nos3)-deficient mice by administration of five low-dose streptozotocin (STZ) injections daily. Groups of diabetic Nos3-/- mice received a CCR2A (30 mg·kg-1·day-1 PF-04634817 in chow) as an early intervention (weeks 2-15 after STZ). The late intervention (weeks 8-15 after STZ) involved PF-04634817 alone, ACEi (captopril in water 10 mg·kg-1·day-1) alone, or combined ACEi + CCR2A. Control diabetic and nondiabetic Nos3-/- mice received normal chow and water. Early intervention with a CCR2A inhibited kidney inflammation and glomerulosclerosis, albuminuria, podocyte loss, and renal function impairment but not hypertension in diabetic Nos3-/- mice. Late intervention with a CCR2A also inhibited kidney inflammation, glomerulosclerosis, and renal dysfunction but did not affect albuminuria. ACEi alone suppressed hypertension and albuminuria and partially reduced podocyte loss and glomerulosclerosis but did not affect renal dysfunction. Compared with ACEi alone, the combined late intervention with ACEi + CCR2A provided better protection against kidney damage (inflammation, glomerulosclerosis, and renal function impairment) but not albuminuria. In conclusion, this study demonstrates that combining CCR2A and ACEi provides broader and superior renal protection than ACEi alone in a model of established diabetic glomerulosclerosis with hypertension.

Effects of combined statin and ACE inhibitor therapy on endothelial function and blood pressure in essential hypertension - a randomised double-blind, placebo controlled crossover study

Background:The aim of this study was to compare the influence of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors on endothelial function and blood pressure in patients with essential hypertension on long-term angiotensin-converting enzyme inhibitor therapy.Method:The study was designed as a prospective, double-blind, randomised, placebo controlled, crossover clinical trial. Twenty patients with essential hypertension were treated with an angiotensin-converting enzyme inhibitor; the control group included 10 healthy subjects. Hypertensive patients received in random order 80 mg of fluvastatin daily or placebo for 6 weeks. The following parameters were assessed at baseline and after each treatment period: serum lipids, flow-mediated vasodilation, activity of von Willebrand factor, concentration of vascular endothelial growth factor, C-reactive protein and 24-hour blood pressure profile.Results:Hypertensive patients did not differ from healthy subjects with respect to age, body mass and biochemical parameters, with the exception of C-reactive protein, which was higher in hypertensive patients (P=0.02). After statin therapy, low-density lipoprotein cholesterol (P<0.0001), C-reactive protein (P=0.03), von Willebrand factor (P=0.03) and vascular endothelial growth factor (P<0.01) decreased and flow-mediated vasodilation improved (P<0.001). Statins had no significant effect on blood pressure.Conclusions:Statins added to angiotensin-converting enzyme inhibitors may improve endothelial function and ameliorate inflammation independently of blood pressure.

Acupuncture therapy for essential hypertension: a network meta-analysis.

To evaluate the efficacy and safety of acupuncture therapies for the treatment of essential hypertension. We performed a systematic electronic search of PubMed, Embase, the Cochrane Library, Chinese Biomedical Literature Database (CBM), Chinese National Knowledge Infrastructure (CNKI), and Wan-fang Data Database. The main outcome indicators measured were the amount of major adverse cardiovascular events (MACE), a change of blood pressure, and the response rate. STATA15.0 software was used for the network meta-analysis. A total of 31 trials with 2,649 patients were included. Patients were allocated to 15 kinds of interventions. These including acupuncture types were electroacupuncture, moxibustion, warm needle therapy, sham acupuncture, behavioral therapy, angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), calcium channel blocker (CCB), beta-blocker, acupuncture combined ACEI, acupuncture combined CCB, acupuncture combined behavior, electroacupuncture combined CCB, and non-treatment. The results of the network meta-analysis showed that there was no significant clinical or statistic difference in systolic blood pressure (SBP) change magnitude between acupuncture treatment and the other 14 therapies. Moxibustion may be better than acupuncture in reducing diastolic blood pressure (DBP) [mean difference (MD): 15.9, 95% confidence interval (CI): 5.96-25.85]. There was no significant difference in reducing DBP between acupuncture and the other 13 interventions. The effective rate of acupuncture combined with AECI [odds ratio (OR) =7.96, 95% CI: 1.11-56.92] and acupuncture combined with behavioral therapy (OR =3.53, 95% CI: 1.08-11.51) in treating hypertension was better than that of acupuncture alone, and there was no statistically significant difference in the effective rate between acupuncture and the other therapies. The existing evidence shows that acupuncture could be used for treating hypertension, and it may have the same effects as common medication. However, due to the low qualities of the original studies, the quality of this evidence is poor. Therefore, it is recommended that more scientific research be performed to confirm the efficacy of acupuncture.

Fixní kombinace inhibitoru ACE a betablokátoru pro srdeční selhání a ICHS

Fixní kombinace dvou léků zlepšuje adherenci/compliance pacientů k léčbě, a vede tak i ke zlepšení kontroly základníhoonemocnění. V případě ischemické choroby srdeční, případně srdečního selhání, je doporučena kombinace s betablokátory.Cosyrel je první fixní kombinace betablokátoru (bisoprolol fumarát) a ACE inhibitoru (perindopril arginin) dostupná na českémtrhu. Preparát je indikován u nemocných s ischemickou chorobou srdeční, hypertenzí a u stabilního srdečního selhání (v dávce5 mg bis/5 mg per, 10 mg bis/5 mg per).

Renal chymase-dependent pathway for angiotensin II formation mediated acute kidney injury in a mouse model of aristolochic acid I-induced acute nephropathy.

Angiotensin-converting enzyme (ACE) is the primary enzyme that converts angiotensin I (Ang I) to angiotensin II (Ang II) in the renin-angiotensin system (RAS). However, chymase hydrates Ang I to Ang II independently of ACE in some kidney diseases, and it may play an important role. The present study investigated whether chymase played a crucial role in aristolochic acid I (AAI)-induced nephropathy. C57BL/6 mice were treated with AAI via intraperitoneal injection for an accumulated AAI dosage of 45 mg/kg body weight (BW) (15 mg/kg BW per day for 3 days). The animals were sacrificed after acute kidney injury development, and blood, urine and kidneys were harvested for biochemical and molecular assays. Mice exhibited increased serum creatinine, BUN and urinary protein after the AAI challenge. Significant infiltrating inflammatory cells and tubular atrophy were observed in the kidneys, and high immunocytokine levels were detected. Renal RAS-related enzyme activities were measured, and a significantly increased chymase activity and slightly decreased ACE activity were observed in the AAI-treated mice. The renal Ang II level reflected the altered profile of RAS enzymes and was significantly increased in AAI-treated mice. Treatment of AAI-induced nephropathic mice with an ACE inhibitor (ACEI) or chymase inhibitor (CI; chymostatin) reduced renal Ang II levels. The combination of ACEI and CI (ACEI+CI) treatment significantly reversed the AAI-induced changes of Ang II levels and kidney inflammation and injuries. AAI treatment significantly increased renal p-MEK without increasing p-STAT3 and p-Smad3 levels, and p-MEK/p-ERK1/2 signalling pathway was significantly activated. CI and ACEI+CI treatments reduced this AAI-activated signaling pathway. AAI-induced nephropathy progression was significantly mitigated with CI and ACEI+CI treatment. This study elucidates the role of RAS in the pathogenesis of AAI-induced nephropathy.

Multi-aspect approach to the optimization of pharmacotherapy of patients with arterial hypertension of high and very high risk

Introduction: Personalization of pharmacotherapy of cardiovascular diseases is one of the urgent problems of cardiology.&#x0D; Material and methods: The study includes 120 patients with grades 2-3 arterial hypertension with the criteria of high and very high risk of developing cardiovascular complications. The patients were randomized into three groups with differentstarting regimens of pharmacotherapy – fixed and free combinations of ACE inhibitors and dihydropyridine CCB. Evaluation of the efficacy, safety and individualization of a therapy was carried out by using pharmacokinetic, pharmacoeconomic, sonographic, and laboratory methods.&#x0D; Results and discussion: Antihypertensive treatment with the inclusion of Amlodipine and Lisinopril or Ramipril in patients with arterial hypertension, having a slow and very slow oxidative metabolism phenotype, is characterized by the development of a more pronounced hypotensive effect in this group of patients (p&lt;0.05-0.001) (Δ% SBP from 12.7 to 24.6 and from 19.6 to 27.9, respectively; Δ% DBP from 10.6 to 19.1 and from 15.9 to 23.6, respectively) in comparison to the group of patients with a fast phenotype (Δ% SBP from 6.42 to 9.34; Δ% DBP from 1.04 to 5.66), which allows administering a personalized pharmacotherapy. For patients with arterial hypertension of high and very high risk, the use of a fixed combination of Amlodipine and Lisinopril as a basic variant of the two-four-component therapy compared with treatment options based on free combinations of the studied drugs provided a significantly more pronounced decrease in systolic blood pressure (24.9%, 17.8 %, 19.0%, respectively, p&lt;0.01), a greater degree of regression of left ventricular myocardial hypertrophy (8.70%, 5.67%, 5.84%, respectively, p&lt;0.05), significant (p&lt;0.05-0.001) improvement in a number of parameters of the patients’ quality of life, and was characterized by the greatest economic efficiency according to various criteria of hypotensive action.&#x0D; Conclusion: The results obtained in the study demonstrate the advantages of a fixed combination over free combinations of antihypertensive drugs and demonstrate the possibility of a pharmacokinetic approach to individualization of pharmacotherapy.

Randomised placebo-controlled trial of combination ACE inhibitor and beta-blocker therapy to prevent cardiomyopathy in children with Duchenne muscular dystrophy? (DMD Heart Protection Study): a protocol study

IntroductionAlthough cardiologists were ‘late-comers’ to the multidisciplinary team—contributing to the complex care of patients with Duchenne muscular dystrophy (DMD), they now recognise the importance of systematic cardiac surveillance and timely...

Association Trends Between Antihypertensive Drug Therapies and Diastolic Hypotension in Emirati Patients with Type 2 Diabetes: A Single-Center Retrospective Longitudinal Study.

IntroductionDiabetes mellitus (DM) is associated with multiple complications, including cardiovascular diseases. Previously, it was believed that the latter are mainly caused by hypertension and increased systolic blood pressure. However, recent studies have challenged this concept, by showing that diastolic dysfunction may also be involved in the cardiovascular events that are associated with DM. Pharmacologic management of hypertension in patients with type 2 DM appears to adversely influence diastolic function.MethodsFour hundred and eight medical records of hypertensive and obese Emirati patients with type 2 DM were included in the present retrospective study. The main objectives of the present study were (1) to determine the prevalence of low diastolic blood pressure (DBP) and diastolic hypotension in this group of patients and (2) to investigate the associations, if any, between the use of various antihypertensive medications and low DBP and diastolic hypotension.ResultsThe results of the present study showed that low DBP (< 70 mmHg) was experienced by 40% of the hypertensive type 2 DM patients, whereas diastolic hypotension (< 60 mmHg) was reported to occur in about 10% of the patients. Another important factor that has been significantly correlated with diastolic hypotension is age (p < 0.01). Association trends have been reported between low DBP and diastolic hypotension and several antihypertensive therapies, including (1) monotherapies such as angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs), (2) dual therapies such as ACE inhibitors in combination with thiazide-like diuretics (THLDs) or beta blockers, and (3) triple therapy combinations of ACE inhibitors with THLDs and potassium-sparing diuretics.ConclusionThe use of antihypertensive medications, in particular ACE inhibitors and ARBs, appears to be a risk factor for the development of low DBP and diastolic hypotension in obese hypertensive Emirati patients with type 2 DM, whereas calcium channel blockers seem to be a safer option for this group of patients.