Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 134
Filter
1.
Eur J Pharmacol ; 973: 176605, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38653362

ABSTRACT

The main objective of this study was to determine if the telmisartan-ameliorative effects of metabolic syndrome (MetS)-evoked nephropathy are attributed to the Hippo pathway. A secondary objective was to investigate the potential of vitamin D3 to enhance telmisartan-favourable effects. A diet composed of 24% fat and 3% salt, along with drinking water containing 10% fructose, was administered for 12 weeks to induce MetS. MetS-rats were given telmisartan (5 mg/kg/day), vitamin D3 (10 µg/kg/day) or both by gavage, starting in the sixth week of experimental diet administration. Assessments performed at closure included renal function, histological examination, catalase, malondialdehyde (MDA), nuclear factor kappa-B (NF-κB), interleukin-6 (IL-6), peroxisome proliferator-activated receptor-γ (PPAR-γ), phosphatase and tensin homolog (PTEN), and transforming growth factor-ß (TGF-ß). Matrix metalloproteinase-9 (MMP-9) immunostaining was conducted. The expression of the Hippo pathway components, as well as that of angiotensin II type 1 and type 2 (AT1 and AT2), receptors was evaluated. Telmisartan attenuated MetS-evoked nephropathy, as demonstrated by improvement of renal function and histological features, enhancement of catalase, reduction of MDA, inflammation (NF-κB, IL-6), and renal fibrosis (increased PPAR-γ and PTEN and reduced MMP-9 and TGF-ß). Telmisartan downregulated AT1-receptor, upregulated AT2-receptor and restored the Hippo pathway. Vitamin D3 replicated most of the telmisartan-elicited effects and enhanced the antifibrotic actions of telmisartan. The alleviative effects of telmisartan on MetS-evoked nephropathy may be related to the restoration of the Hippo pathway. The combination of vitamin D3 and telmisartan exerted more favourable effects on metabolic and nephropathic biomarkers compared with either one administered alone.


Subject(s)
Hippo Signaling Pathway , Kidney Diseases , Kidney , Metabolic Syndrome , Telmisartan , Animals , Telmisartan/pharmacology , Telmisartan/therapeutic use , Metabolic Syndrome/drug therapy , Metabolic Syndrome/metabolism , Metabolic Syndrome/complications , Metabolic Syndrome/pathology , Male , Rats , Kidney Diseases/drug therapy , Kidney Diseases/metabolism , Kidney Diseases/pathology , Kidney/drug effects , Kidney/pathology , Kidney/metabolism , Signal Transduction/drug effects , Protein Serine-Threonine Kinases/metabolism , NF-kappa B/metabolism , Cholecalciferol/pharmacology , Cholecalciferol/therapeutic use , Rats, Wistar , Matrix Metalloproteinase 9/metabolism , PTEN Phosphohydrolase/metabolism , PPAR gamma/metabolism , Oxidative Stress/drug effects , Receptor, Angiotensin, Type 1/metabolism , Receptor, Angiotensin, Type 2/metabolism , Malondialdehyde/metabolism , Interleukin-6/metabolism , Benzimidazoles/pharmacology , Benzimidazoles/therapeutic use
2.
ACS Biomater Sci Eng ; 10(3): 1517-1529, 2024 Mar 11.
Article in English | MEDLINE | ID: mdl-38377553

ABSTRACT

The etiology of diabetic nephropathy (DN) is complex, and the incidence is increasing year by year. The patient's kidney showed oxidative stress damage, increasing active oxygen species (ROS) content, and vasoconstriction. Due to poor drug solubility and low renal accumulation, the current treatment regimens have not effectively alleviated glomerulopathy and other kidney damage caused by DN. Therefore, it is of great significance to explore new treatment strategies and drug delivery systems. Here, we constructed an oral nanodelivery system (Tel/CAN@CS-DA) that reduced oxidative stress and vasoconstriction. Deoxycholic acid (DA)-modified nanoparticles entered into intestinal epithelial cells (Caco2 cells) via the bile acid biomimetic pathway, then escaped from the lysosomes and eventually spat out the cells, increasing the oral absorption of nanoparticles. Chitosan (CS) nanoparticles could achieve renal targeting through specific binding with a renal giant protein receptor and deliver drugs to renal tubule epithelial cells (HK-2 cells). In vitro studies also proved that telmisartan (Tel) and canagliflozin (CAN) effectively removed cellular reactive oxygen species (ROS) and reduced HK-2 cell apoptosis caused by high glucose. In the in vivo model induced by streptozotocin (STZ), the results showed that the nanosystem not only elevated AMPK protein expression, inhibited angiotensin II (Ang II) protein expression to effectively reduce oxidative stress level, dilated renal blood vessels but also reduced the degree of inflammation and fibrosis. Overall, Tel/CAN@CS-DA multifunctional oral nanosystem can effectively treat DN with low toxicity, which provides a new idea for the treatment of DN.


Subject(s)
Diabetes Mellitus, Experimental , Diabetic Nephropathies , Animals , Humans , Diabetic Nephropathies/drug therapy , Diabetic Nephropathies/etiology , Diabetic Nephropathies/metabolism , Reactive Oxygen Species/metabolism , Caco-2 Cells , Vasoconstriction , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Experimental/complications , Oxidative Stress , Telmisartan/pharmacology , Telmisartan/therapeutic use , Intestinal Absorption
3.
Int J Nanomedicine ; 19: 1487-1508, 2024.
Article in English | MEDLINE | ID: mdl-38380147

ABSTRACT

Background: Radiation stimulates the secretion of tumor stroma and induces resistance, recurrence, and metastasis of stromal-vascular tumors during radiotherapy. The proliferation and activation of tumor-associated fibroblasts (TAFs) are important reasons for the production of tumor stroma. Telmisartan (Tel) can inhibit the proliferation and activation of TAFs (resting TAFs), which may promote radiosensitization. However, Tel has a poor water solubility. Methods: In this study, self-assembled telmisartan nanoparticles (Tel NPs) were prepared by aqueous solvent diffusion method to solve the insoluble problem of Tel and achieve high drug loading of Tel. Then, erythrocyte membrane (ECM) obtained by hypotonic lysis was coated on the surface of Tel NPs (ECM/Tel) for the achievement of in vivo long circulation and tumor targeting. Immunofluorescence staining, western blot and other biological techniques were used to investigate the effect of ECM/Tel on TAFs activation inhibition (resting effect) and mechanisms involved. The multicellular spheroids (MCSs) model and mouse breast cancer cells (4T1) were constructed to investigate the effect of ECM/Tel on reducing stroma secretion, alleviating hypoxia, and the corresponding promoting radiosensitization effect in vitro. A mouse orthotopic 4T1 breast cancer model was constructed to investigate the radiosensitizing effect of ECM/Tel on inhibiting breast cancer growth and lung metastasis of breast cancer. Results: ECM/Tel showed good physiological stability and tumor-targeting ability. ECM/Tel could rest TAFs and reduce stroma secretion, alleviate hypoxia, and enhance penetration in tumor microenvironment. In addition, ECM/Tel arrested the cell cycle of 4T1 cells to the radiosensitive G2/M phase. In mouse orthotopic 4T1 breast cancer model, ECM/Tel played a superior role in radiosensitization and significantly inhibited lung metastasis of breast cancer. Conclusion: ECM/Tel showed synergistical radiosensitization effect on both the tumor microenvironment and tumor cells, which is a promising radiosensitizer in the radiotherapy of stroma-vascular tumors.


Subject(s)
Lung Neoplasms , Vascular Neoplasms , Mice , Animals , Telmisartan/pharmacology , Telmisartan/therapeutic use , Erythrocyte Membrane , Lung Neoplasms/drug therapy , Radiation Tolerance , Hypoxia , Cell Line, Tumor , Tumor Microenvironment
4.
J Clin Hypertens (Greenwich) ; 26(3): 262-273, 2024 03.
Article in English | MEDLINE | ID: mdl-38319595

ABSTRACT

This study aimed to compare and evaluate the efficacy of the blood pressure (BP) control and cholesterol-lowering effects and safety of combination therapy with telmisartan, rosuvastatin, and ezetimibe versus rosuvastatin and ezetimibe double therapy or telmisartan single therapy in dyslipidemia patients with hypertension. After a wash-out/therapeutic lifestyle change period of ≥4 weeks, a total of 100 eligible patients were randomized and received one of three treatments for 8 weeks: (1) telmisartan 80 mg/rosuvastatin 20 mg/ezetimibe 10 mg (TRE), (2) rosuvastatin 20 mg/ezetimibe 10 mg (RE), or (3) telmisartan 80 mg (T). The primary endpoint was the efficacy evaluation of TRE by comparing changes in mean sitting systolic blood pressure (msSBP) and mean percentage change in low-density lipoprotein-C (LDL-C) from baseline after 8 weeks of treatment. The least square (LS) mean (SE) changes in msSBP at 8 weeks compared with baseline were -23.02 (3.04) versus -7.18 (3.09) mmHg in the TRE and RE groups, respectively (p < .0001), and -25.80 (2.74) versus -14.92 (2.65) mmHg in the TRE and T groups, respectively (p = .0005). The percentage changes in the mean (SD) LDL-C at 8 weeks compared with baseline were -54.97% (3.49%) versus -0.17% (3.23%) in the TRE and T groups, respectively (p < .0001). No serious adverse events occurred, and no statistically significant differences in the incidence of overall AEs and adverse drug reactions occurred among the three groups. TRE therapy significantly decreased msSBP and LDL-C compared to RE or T therapy with comparable safety and tolerability profiles.


Subject(s)
Dyslipidemias , Ezetimibe , Hypertension , Rosuvastatin Calcium , Telmisartan , Humans , Anticholesteremic Agents/therapeutic use , Cholesterol, LDL , Double-Blind Method , Drug Therapy, Combination/adverse effects , Dyslipidemias/drug therapy , Ezetimibe/therapeutic use , Hypertension/drug therapy , Rosuvastatin Calcium/therapeutic use , Telmisartan/therapeutic use , Treatment Outcome , Antihypertensive Agents/therapeutic use
5.
Am J Hypertens ; 37(6): 429-437, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38285627

ABSTRACT

BACKGROUND: Telmisartan exhibits superior efficacy in controlling 24-h blood pressure (BP) compared with other angiotensin receptor blockers (ARBs). However, data on its cardiovascular effects in patients with hypertension are limited. This study aimed to evaluate the cardiovascular outcomes in patients taking telmisartan compared to those taking other ARBs. METHODS: This multicenter retrospective study used data from the Korea University Medical Center database, built from electronic health records. A total of 19,247 patients taking two or more antihypertensive medications were identified. Patients prescribed telmisartan (telmisartan users) were compared with those prescribed an ARB other than telmisartan (other ARB users). The primary outcome was major adverse cardiac events (MACE), a composite of cardiovascular death, myocardial infarction, stroke, and hospitalizations due to heart failure. The adjusted outcomes were compared using 1:1 propensity score (PS) matching. RESULTS: Overall, 3,437 (17.9%) patients were telmisartan users. These patients were more likely to be younger and male and less likely to have a history of chronic kidney disease, dialysis, or heart failure. In the PS-matched cohort, BP control was similar in both groups; however, telmisartan users exhibited significantly lower visit-to-visit BP variability. The adjusted 3-year MACE rate was similar between telmisartan users (4.6%) and other ARB users (4.7%, log-rank P = 0.75), with comparable safety profiles. CONCLUSIONS: In real-world practice, telmisartan showed cardiovascular outcomes similar to those of other ARBs in patients with hypertension taking two or more antihypertensive drugs.


Subject(s)
Angiotensin II Type 1 Receptor Blockers , Electronic Health Records , Hypertension , Telmisartan , Humans , Telmisartan/therapeutic use , Male , Female , Hypertension/drug therapy , Hypertension/physiopathology , Hypertension/mortality , Hypertension/epidemiology , Retrospective Studies , Middle Aged , Aged , Republic of Korea/epidemiology , Treatment Outcome , Angiotensin II Type 1 Receptor Blockers/therapeutic use , Angiotensin II Type 1 Receptor Blockers/adverse effects , Antihypertensive Agents/therapeutic use , Antihypertensive Agents/adverse effects , Blood Pressure/drug effects , Time Factors , Cardiovascular Diseases/mortality , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/prevention & control , Risk Factors
6.
Minerva Cardiol Angiol ; 72(2): 102-110, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38231079

ABSTRACT

BACKGROUND: The potential influence of renin-angiotensin inhibitors on the severity of SARS-CoV-2 infection has been considered in preclinical and observational studies with contradictory results. Therefore, we investigated the effect of telmisartan in reducing lung injury among hospitalized COVID-19 patients. METHODS: The STAR-COVID trial was conducted as a prospective, parallel-group, randomized, open-label study involving hospitalized adult patients with severe COVID-19 (NCT04510662). Sixty-six patients were enrolled: 33 were assigned to the telmisartan group and 33 to the control group. The mean age of participants was 48.8 years, with 62.5% being male. Participants were randomly assigned in a 1:1 ratio to receive either telmisartan (40 mg daily for 14 days or until discharge) plus standard of care or standard of care alone. The primary outcome assessed was the initiation of mechanical ventilation within 14 days. Secondary outcomes included 30-day mortality, the need for vasopressors, hemodialysis requirements, and length of hospital stay. RESULTS: Comparison between the telmisartan group and the control group revealed no significant difference in the occurrence of mechanical ventilation at 14 days (25% with telmisartan vs. 18.7% with control, P=0.579). Additionally, there were no significant differences observed in terms of mortality (25% vs. 21.9%, P=0.768), the need for vasopressors (18.8% in both groups, P=1.000), hemodialysis requirements (6.3% vs. 3.1%, P=0.500), and length of hospital stay (median of 7 days in both groups, P=0.962). CONCLUSIONS: Compared with the standard of care, telmisartan therapy demonstrated no significant impact on respiratory failure in hospitalized patients with severe COVID-19.


Subject(s)
COVID-19 , Respiratory Insufficiency , Adult , Humans , Male , Middle Aged , Female , COVID-19/complications , Telmisartan/therapeutic use , SARS-CoV-2 , Prospective Studies , Standard of Care , Respiratory Insufficiency/drug therapy
9.
Ter Arkh ; 95(9): 810-817, 2023 Nov 03.
Article in Russian | MEDLINE | ID: mdl-38158926

ABSTRACT

The activity of the renin-angiotensin-aldosterone system is one of the main pathogenetic mechanisms underlying cardiovascular diseases at all stages of the cardiovascular continuum. This article discusses the role of telmisartan and azilsartan as the most powerful sartans in modern cardiology. Azilsartan and especially telmisartan have a significant organoprotection and are superior to other antihypertensive drugs in terms of lowering blood pressure. However, the effect of azilsartan on hard endpoints has not been studied while the efficacy of telmisartan on hard endpoints has been evaluated in plenty clinical trials including 3 large randomized clinical trials with several thousand patients. The article also presents calculations showing the better cost-effectiveness of telmisartan compared to azilsartan.


Subject(s)
Angiotensin II Type 1 Receptor Blockers , Hypertension , Humans , Telmisartan/pharmacology , Telmisartan/therapeutic use , Angiotensin II Type 1 Receptor Blockers/pharmacology , Angiotensin II Type 1 Receptor Blockers/therapeutic use , Hypertension/drug therapy , Benzimidazoles/pharmacology , Benzimidazoles/therapeutic use , Antihypertensive Agents/pharmacology , Antihypertensive Agents/therapeutic use , Blood Pressure
10.
Medicine (Baltimore) ; 102(46): e36098, 2023 Nov 17.
Article in English | MEDLINE | ID: mdl-37986329

ABSTRACT

There is a lack of studies comparing the risk of cardio-cerebrovascular disease between angiotensin receptor blockers (ARBs) of different half-lives. We aimed to compare the risks of myocardial infarction (MI), heart failure (HF), and cerebrovascular disease with the use of valsartan, losartan, irbesartan, and telmisartan with different half-lives in a national claim-based retrospective cohort of patients aged ≥ 40 years with hypertension. To establish a cohort exposed to valsartan, losartan, irbesartan, or telmisartan, we performed propensity score (PS) matching and used an as-treated approach to evaluate exposure. The Cox regression model was employed to calculate hazard ratios, which were based on the incidence rate for each newly occurring event of MI, heart failure, or cerebrovascular disease. These hazard ratios were calculated to compare the risk of MI, heart failure, and cerebrovascular disease associated with valsartan, losartan, and irbesartan in comparison to telmisartan. A PS-matched cohort of 148,229 patients was established for each of valsartan, losartan, irbesartan, or telmisartan. The matched cohort analysis showed that the adjusted hazard ratio (aHRs, 95% confidence interval) for MI was higher for valsartan use (1.39, 1.33-1.45) and losartan use (1.10, 1.05-1.15) but lower for irbesartan use (0.90, 0.86-0.94) compared with the reference (telmisartan). The aHRs for HF were not different among these ARBs (angiotensin receptor blockers). The aHR for cerebrovascular disease was lower for valsartan use (0.85, 0.83-0.87) and losartan use (0.80, 0.78-0.82) but higher for irbesartan use (1.11, 1.09-1.13) compared with the reference. We found differences in the risk of MI and cerebrovascular disease with the use of different ARBs compared to telmisartan use. Valsartan, and losartan with a short half-life, which showed a higher risk of MI, had a lower risk of cerebrovascular disease. Conversely, irbesartan with a long half-life, which showed a lower risk of MI, had a higher risk of cerebrovascular disease.


Subject(s)
Cerebrovascular Disorders , Heart Failure , Myocardial Infarction , Humans , Losartan/adverse effects , Irbesartan/adverse effects , Telmisartan/therapeutic use , Valsartan/therapeutic use , Angiotensin Receptor Antagonists , Retrospective Studies , Tetrazoles/adverse effects , Biphenyl Compounds , Benzimidazoles/adverse effects , Angiotensin-Converting Enzyme Inhibitors , Heart Failure/epidemiology , Myocardial Infarction/chemically induced , Myocardial Infarction/epidemiology , Cerebrovascular Disorders/epidemiology
11.
Int Immunopharmacol ; 124(Pt B): 110995, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37801970

ABSTRACT

As angiotensin II is associated with inflammation, type I angiotensin II receptor blockers (ARBs) exibit anti-inflammatory effects in patients with hypertension as well as inflammatory disease animal models including arthritis models. The present study aimed to investigate whether ARBs exert anti-inflammatory effects in vivo in skin disorders. We tested effects of ARBs on 1-chloro-2,4-dinitrobenzene(CDNB)-induced atopic dermatitis-like and imiquimod-induced psoriasis-like skin models. CDNB-induced atopic dermatitis-like skin lesions were suppressed by administration of candesartan or telmisartan. The suppressive effect of telmisartan was blocked by the presence of GW9662, a selective PPARγ inhibitor, but not that of candesartan. Both ARBs suppressed increases in pro-inflammatory cytokine (IL-4, IL-13, IFN-γ, and IL-17A) levels, and GW9662 inhibited telmisartan-induced suppression but not candesartan. Candesartan significantly inhibited in vitro differentiation of naïve T cells into Th17 cells to a greater extent than telmisartan. In the imiquimod-induced psoriasis model, whose primary etiology is activation of IL-23/IL-17 axis, candesartan significantly suppressed psoriasis-like skin lesions and Th17 cell populations in both lymph nodes and spleens to a greater extent than telmisartan. Overall, certain ARBs may have anti-inflammatory effects in skin diseases. Candesartan may have therapeutic implications in inflammatory skin disorders by suppressing Th17 differentiation, while telmisartan might have therapeutic potential by activating PPARγ.


Subject(s)
Dermatitis, Atopic , Psoriasis , Animals , Humans , Telmisartan/therapeutic use , Th17 Cells , Angiotensin II Type 1 Receptor Blockers/pharmacology , Angiotensin II Type 1 Receptor Blockers/therapeutic use , Dermatitis, Atopic/drug therapy , Angiotensin Receptor Antagonists , PPAR gamma , Imiquimod/therapeutic use , Benzoates/pharmacology , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Skin/pathology , Psoriasis/chemically induced , Psoriasis/drug therapy , Psoriasis/pathology , Cell Differentiation , Anti-Inflammatory Agents/therapeutic use
12.
Mol Pharm ; 20(9): 4758-4769, 2023 09 04.
Article in English | MEDLINE | ID: mdl-37585079

ABSTRACT

Hepatocellular carcinoma (HCC) is the leading cause of cancer-related mortality worldwide. Telmisartan (TLM), a BSC class II drug, has been reported to have antiproliferative activity in HCC. However, its therapeutic activity is limited by poor bioavailability and unpredictable distribution. This work aimed to enhance TLM's liver uptake for HCC management through passive and active targeting pathways utilizing chitosan nanoparticles decorated with lactose (LCH NPs) as a delivery system. In vitro cell cytotoxicity and cellular uptake studies indicated that TLM-LCH NPs significantly (p < 0.05) enhanced the antiproliferative activity and cellular uptake percentage of TLM. In vivo bioavailability and liver biodistribution studies indicated that TLM-LCH NPs significantly (p < 0.05) enhanced TLM concentrations in plasma and the liver. The relative liver uptake of TLM from TLM-LCH NPs was 2-fold higher than that of unmodified NPs and 5-fold higher than that of plain TLM suspension. In vivo studies of a N-nitrosodiethylamine-induced HCC model revealed that administration of TLM through LCH NPs improved liver histology and resulted in lower serum alpha-fetoprotein (AFP), matrix metalloproteinase 2 (MMP-2), vascular endothelial growth factor (VEGF) levels, and liver weight index compared to plain TLM and TLM-loaded unmodified NPs. These results reflected the high potentiality of LCH NPs as a liver-targeted delivery system for TLM in the treatment of HCC.


Subject(s)
Carcinoma, Hepatocellular , Chitosan , Liver Neoplasms , Nanoparticles , Animals , Mice , Humans , Carcinoma, Hepatocellular/chemically induced , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/metabolism , Liver Neoplasms/chemically induced , Liver Neoplasms/drug therapy , Liver Neoplasms/metabolism , Telmisartan/therapeutic use , Chitosan/metabolism , Diethylnitrosamine , Matrix Metalloproteinase 2/metabolism , Vascular Endothelial Growth Factor A/metabolism , Tissue Distribution , Hep G2 Cells
13.
Curr Probl Cardiol ; 48(11): 101984, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37473946

ABSTRACT

The BRASH (bradycardia, renal failure, atrioventricular block, shock, and hyperkalaemia) syndrome is a recently recognized condition which may lead to life-threatening complications if not correctly identified and treated early. We report here the case of a 74-year-old woman with type 2 diabetes, hypertension and atrial flutter who presented to the emergency department with 2-day history of dizziness, presyncope, and bradycardia, and a junctional rhythm at 61 beat per minute on initial ECG. She was on apixaban, digoxin, prazosin, and telmisartan. Serum biochemistry revealed severe hyperkalaemia with a potassium 8.4 mmol/L, creatinine 161 mmol/L, glucose 15.3 mmol/L and an upper normal digoxin level of 1.2 mmol/L (ref. 0.6-1.2). Arterial blood pH was 7.2. Given the constellation of biochemical and clinical findings a diagnosis of BRASH syndrome was made, though her blood pressure values at presentation were rather high (180/65-179/59 mmHg). The patient was rapidly stabilised with the administration of intravenous insulin and dextrose, fluid resuscitation, and zirconium cyclosilicate (SZC), followed by haemodialysis. Following the correction of the serum potassium to 4.7 mmol/L, a further ECG performed 6 hours later, showed a restoration of sinus rhythm with a rate of 65 bpm, normalization of the QRS duration. The digoxin and telmisartan were discontinued, and the patient was commenced on a calcium channel antagonist for hypertension. Clinicians should be alerted to patients who present with either a BRASH (shock) or BRAHH (hypertensive manifestation) where timely intervention is essential to avoid life-threatening brady-and tachyarrhythmias in these patients.


Subject(s)
Diabetes Mellitus, Type 2 , Hyperkalemia , Hypertension , Aged , Female , Humans , Arrhythmias, Cardiac , Bradycardia/complications , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/diagnosis , Digoxin/therapeutic use , Hyperkalemia/drug therapy , Hyperkalemia/etiology , Potassium/therapeutic use , Telmisartan/therapeutic use
14.
Clin Cardiol ; 46(8): 886-898, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37432701

ABSTRACT

This study aimed to evaluate the efficacy of single-pill combination (SPC) antihypertensive drugs in patients with uncontrolled essential hypertension. Through Searching Pubmed, EMBASE, the Cochrane Library, and Web of Science collected only randomized controlled trials on the efficacy of single-pill combination antihypertensive drugs in people with uncontrolled essential hypertension. The search period is from the establishment of the database to July 2022. The methodological quality of the included studies was assessed using the Cochrane Risk of Bias Assessment, and statistical analyses were performed using Review Manage 5.3 and Stata 15.1 software. This review ultimately included 32 references involving 16 273 patients with uncontrolled essential hypertension. The results of the network meta-analysis showed that a total of 11 single-pill combination antihypertensive drugs were included, namely: Amlodipine/valsartan, Telmisartan/amlodipine, Losartan/HCTZ, Candesartan/HCTZ, Amlodipine/benazepril, Telmisartan/HCTZ, Valsartan/HCTZ, Irbesartan/amlodipine, Amlodipine/losartan, Irbesartan/HCTZ, and Perindopril/amlodipine. According to SUCRA, Irbesartan/amlodipine may rank first in reducing systolic blood pressure (SUCRA: 92.2%); Amlodipine/losartan may rank first in reducing diastolic blood pressure (SUCRA: 95.1%); Telmisartan/amlodipine may rank first in blood pressure control rates (SUCRA: 83.5%); Amlodipine/losartan probably ranks first in diastolic response rate (SUCRA: 84.5%). Based on Ranking Plot of the Network, we can conclude that single-pill combination antihypertensive drugs are superior to monotherapy, and ARB/CCB combination has better advantages than other SPC in terms of systolic blood pressure, diastolic blood pressure, blood pressure control rate, and diastolic response rate. However, due to the small number of some drug studies, the lack of relevant studies has led to not being included in this study, which may impact the results, and readers should interpret the results with caution.


Subject(s)
Antihypertensive Agents , Hypertension , Humans , Antihypertensive Agents/therapeutic use , Losartan/pharmacology , Losartan/therapeutic use , Hypertension/diagnosis , Hypertension/drug therapy , Telmisartan/pharmacology , Telmisartan/therapeutic use , Irbesartan/pharmacology , Irbesartan/therapeutic use , Angiotensin Receptor Antagonists/therapeutic use , Network Meta-Analysis , Hydrochlorothiazide/adverse effects , Valine/adverse effects , Drug Therapy, Combination , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Amlodipine/therapeutic use , Valsartan/therapeutic use , Tetrazoles/therapeutic use , Blood Pressure , Essential Hypertension/diagnosis , Essential Hypertension/drug therapy , Essential Hypertension/chemically induced
15.
Diabetes Obes Metab ; 25(11): 3152-3160, 2023 11.
Article in English | MEDLINE | ID: mdl-37417375

ABSTRACT

AIM: To evaluate the effect of four different drug classes on soluble urokinase plasminogen activator receptor (suPAR), a biomarker active in multiple inflammatory processes and a risk factor for complications, in people with type 1 and type 2 diabetes. METHODS: We conducted post hoc analyses of a randomized, open-label, crossover trial including 26 adults with type 1 and 40 with type 2 diabetes with urinary albumin-creatinine ratio ≥30 and ≤500 mg/g assigned to 4-week treatments with telmisartan 80 mg, empagliflozin 10 mg, linagliptin 5 mg and baricitinib 2 mg, separated by 4-week washouts. Plasma suPAR was measured before and after each treatment. SuPAR change after each treatment was calculated and, for each individual, the best suPAR-reducing drug was identified. Subsequently, the effect of the best individual drug was compared against the mean of the other three drugs. Repeated-measures linear mixed-effects models were employed. RESULTS: The baseline median (interquartile range) plasma suPAR was 3.5 (2.9, 4.3) ng/mL. No overall effect on suPAR levels was observed for any one drug. The individual best-performing drug varied, with baricitinib being selected for 20 participants (30%), followed by empagliflozin for 19 (29%), linagliptin for 16 (24%) and telmisartan for 11 (17%). The individual best-performing drug reduced suPAR by 13.3% (95% confidence interval [CI] 3.7, 22.8; P = 0.007). The difference in suPAR response between the individual best-performing drug and the other three was -19.7% (95% CI -23.1, -16.3; P < 0.001). CONCLUSIONS: We demonstrated no overall effect of 4-week treatment with telmisartan, empagliflozin, linagliptin or baricitinib on suPAR. However, individualization of treatment might significantly reduce suPAR levels.


Subject(s)
Diabetes Mellitus, Type 1 , Diabetes Mellitus, Type 2 , Receptors, Urokinase Plasminogen Activator , Adult , Humans , Biomarkers , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/metabolism , Linagliptin/therapeutic use , Receptors, Urokinase Plasminogen Activator/drug effects , Telmisartan/therapeutic use , Diabetes Mellitus, Type 1/drug therapy , Diabetes Mellitus, Type 1/metabolism
17.
J Alzheimers Dis ; 94(3): 919-933, 2023.
Article in English | MEDLINE | ID: mdl-37355897

ABSTRACT

BACKGROUND: Alzheimer's disease (AD) is the most common type of neurodegenerative disorder. There are few effective medications for halting the progression of AD. Telmisartan (TEL) is a widely used anti-hypertensive drug approved by FDA. Aside from treating hypertension, TEL has been revealed to provide protection against AD. However, the underlying mechanisms remain unclear. OBJECTIVE: To investigate the mechanisms underlying the beneficial effects of TEL against AD. METHODS: Eight-month-old APP/PS1 mice were administered with 5 mg/kg TEL once per day for 4 successive months. Nesting test, Y-maze test, and Morris water maze test were employed to assess the cognitive and executive functions. Neuronal and synaptic markers, amyloid-ß (Aß) pathology, neuroinflammation, and oxidative stress in the brains were measured. Specifically, components involved in Aß production and degradation pathway were analyzed to explore the mechanisms underlying the therapeutic effect of TEL against Aß pathology. The primary microglia were used to uncover the mechanisms underlying the anti-inflammatory effects of TEL in AD. Additionally, the preventive effect of TEL against AD were investigated using 4-month-old APP/PS1 mice. RESULTS: TEL treatment ameliorated cognitive and executive impairments, neuronal and synaptic injury, Aß pathology, neuroinflammation, and oxidative stress in APP/PS1 mice. The favorable effects of TEL on Aß pathology were achieved by inhibiting enzymatic Aß production and facilitating enzymatic and autophagic Aß degradation. Meanwhile, the anti-inflammatory effects of TEL were accomplished via microglial PPARγ/NLRP3 pathway. The administration of TEL prior to symptom onset prevented AD-related cognitive decline and neuropathologies. CONCLUSION: TEL represents a promising agent for AD prevention and treatment.


Subject(s)
Alzheimer Disease , Cognitive Dysfunction , Mice , Animals , Alzheimer Disease/complications , Alzheimer Disease/drug therapy , Alzheimer Disease/metabolism , Telmisartan/therapeutic use , Amyloid beta-Protein Precursor/genetics , Amyloid beta-Protein Precursor/metabolism , Mice, Transgenic , Neuroinflammatory Diseases , Cognitive Dysfunction/drug therapy , Cognitive Dysfunction/etiology , Cognitive Dysfunction/metabolism , Amyloid beta-Peptides/metabolism , Anti-Inflammatory Agents/therapeutic use , Disease Models, Animal
18.
Int J Mol Sci ; 24(9)2023 Apr 27.
Article in English | MEDLINE | ID: mdl-37175678

ABSTRACT

Despite the large arsenal of analgesic medications, neuropathic pain (NP) management is not solved yet. Angiotensin II receptor type 1 (AT1) has been identified as a potential target in NP therapy. Here, we investigate the antiallodynic effect of AT1 blockers telmisartan and losartan, and particularly their combination with morphine on rat mononeuropathic pain following acute or chronic oral administration. The impact of telmisartan on morphine analgesic tolerance was also assessed using the rat tail-flick assay. Morphine potency and efficacy in spinal cord samples of treated neuropathic animals were assessed by [35S]GTPγS-binding assay. Finally, the glutamate content of the cerebrospinal fluid (CSF) was measured by capillary electrophoresis. Oral telmisartan or losartan in higher doses showed an acute antiallodynic effect. In the chronic treatment study, the combination of subanalgesic doses of telmisartan and morphine ameliorated allodynia and resulted in a leftward shift in the dose-response curve of morphine in the [35S]GTPγS binding assay and increased CSF glutamate content. Telmisartan delayed morphine analgesic-tolerance development. Our study has identified a promising combination therapy composed of telmisartan and morphine for NP and opioid tolerance. Since telmisartan is an inhibitor of AT1 and activator of PPAR-γ, future studies are needed to analyze the effect of each component.


Subject(s)
Analgesics, Opioid , Neuralgia , Rats , Animals , Analgesics, Opioid/therapeutic use , Telmisartan/pharmacology , Telmisartan/therapeutic use , Losartan/therapeutic use , Guanosine 5'-O-(3-Thiotriphosphate) , Drug Tolerance , Analgesics/pharmacology , Analgesics/therapeutic use , Morphine/pharmacology , Morphine/therapeutic use , Neuralgia/drug therapy , Glutamates/therapeutic use
20.
Bratisl Lek Listy ; 124(5): 380-386, 2023.
Article in English | MEDLINE | ID: mdl-36876369

ABSTRACT

OBJECTIVE: We performed this meta-analysis determining the antihypertensive effect of telmisartan versus perindopril in patients with essential hypertension. BACKGROUND: The comparison of antihypertensive effects between telmisartan and perindopril were controversial. METHODS: Pubmed, Web of Science, and Cochrane Central were searched for all published studies. RESULTS: The antihypertensive effects were assessed in 753 patients included in 7 trials with a mean follow-up of 20 ± 16 weeks. There was no significant difference between telmisartan and perindopril in reduction of systolic blood pressure (SBP, weighted mean differences (WMD) 0.02 (95% confidence interval (CI), ‒2.78, 2.81) mm Hg, p > 0.05). The reduction of diastolic BP (DBP) treated with telmisartan was greater than perindopril in these patients (WMD ‒2.05 (95% CI, ‒2.60, ‒1.49) mm Hg, p < 0.001). Considering the effects of different doses on BP reduction, a sub-analysis was performed. The reduction of DBP treated with 40 mg/day telmisartan was greater than 4‒5 mg/day perindopril (WMD ‒2.18 (95% CI, ‒2.83, ‒1.53) mm Hg, p 0.05). CONCLUSION: The reduction of DBP is greater treated with telmisartan than perindopril in patients with essential hypertension (Tab. 2, Fig. 4, Ref. 34). Text in PDF www.elis.sk Keywords: essential hypertension, blood pressure, telmisartan, perindopril, meta-analysis.


Subject(s)
Antihypertensive Agents , Hypertension , Humans , Antihypertensive Agents/pharmacology , Telmisartan/therapeutic use , Perindopril/adverse effects , Benzimidazoles/adverse effects , Essential Hypertension
SELECTION OF CITATIONS
SEARCH DETAIL
...