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1.
Talanta ; 277: 126400, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38876031

RESUMO

Captopril (CP) is commonly used as an active enzyme inhibitor for the treatment of coronary heart disease, hypertension and angina pectoris. The development of sensitive and efficient method for CP analysis is of great importance in biomedical research. Herein, we fabricated a sensitive and robust hydrogel-assisted paper-based sensor based on fluorescence UiO-66-NH2@ZIF-8 and Co, N-doped carbon nanozymes with oxidase-mimicking activity for accurate monitoring of captopril. The hydrogel-assisted paper-based sensor appeared a visible pink signal due to the catalytic oxidation of colorless N,N-diethyl-p-phenylenediamine (DPD) to oxDPD by Co, N-doped carbon-based nanozymes, and resulted in the fluorescence quenching of UiO-66-NH2@ZIF-8. In the presence of captopril, the oxidation of chromogenic substrate DPD by Co, N-doped nanozymes in the hydrogel-assisted paper-based sensor was hindered and accompanied by a change in the visible color, leading to recovery of the fluorescence of UiO-66-NH2@ZIF-8, and the change in the fluorescence color could also be observed. Therefore, the quantitative detection of captopril is achieved by taking a smartphone photograph and converting the image parameters into data information using ImageJ software. The portable hydrogel-assisted paper sensor provided sensitive detection of captopril in two modes based on visible color change as well as fluorescence color change with limits of detection of 0.45 µM and 0.47 µM, respectively. This hydrogel-assisted paper-based sensor has been successfully applied to the accurate monitoring of captopril in human serum, providing a potential avenue for in situ detection of captopril.

2.
Int J Biol Macromol ; 274(Pt 2): 133289, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38908639

RESUMO

Captopril is a thiol drug, widely used for the management of hypertension and cardiovascular diseases. Reactive thiols are found to covalently modify the cysteines of plasma proteins and affect their structure and function. Human serum albumin (HSA) is prone to undergo modification by various low molecular weight compounds, including drugs. Cysteine34 (Cys34) in HSA has a free thiol group with antioxidant properties, considered to be the most redox-sensitive amino acid in plasma. Through mass-spectrometric analysis, we demonstrate for the first time that captopril forms a disulfide adduct at Cys34 residue and increases the protease susceptibility of HSA to trypsin. As evidenced by our biophysical and electron microscopy studies, HSA undergoes structural alteration, aggregation and morphological changes when treated with different captopril concentrations. Molecular dynamics studies further revealed the regions of secondary structural changes in HSA due to disulfide adduct formation by captopril at Cys34. It also elucidated the residues involved in the noncovalent interactions with captopril. It is envisaged that structural change in HSA may influence the efficacy of drug delivery as well as its own biological function. These findings may thus provide significant insights into the field of pharmacology intriguing further investigation into the effects of long-term captopril treatment.

3.
Mikrochim Acta ; 191(7): 374, 2024 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-38847878

RESUMO

The combination of silica nanoparticles with fluorescent molecularly imprinted polymers (Si-FMIPs) prepared by a one-pot sol-gel synthesis method to act as chemical sensors for the selective and sensitive determination of captopril is described. Several analytical parameters were optimized, including reagent ratio, solvent, concentration of Si-FMIP solutions, and contact time. Fourier-transform infrared spectroscopy (FT-IR), transmission electron microscopy (TEM), and the ninhydrin assay were used for characterization. The selectivity was evaluated against molecules belonging to other drug classes, such as fluoroquinolones, nonacid nonopioids, benzothiadiazine, alpha amino acids, and nitroimidazoles. Under optimized conditions, the Si-FMIP-based sensor exhibited a working range of 1-15 µM, with a limit of detection (LOD) of 0.7 µM, repeatability of 6.4% (n = 10), and suitable recovery values at three concentration levels (98.5% (1.5 µM), 99.9% (3.5 µM), and 99.2% (7.5 µM)) for wastewater samples. The sensor provided a working range of 0.5-15 µM for synthetic urine samples, with an LOD of 0.4 µM and a repeatability of 7.4% (n = 10) and recovery values of 93.7%, 92.9%, and 98.0% for 1.0 µM, 3.5 µM, and 10 µM, respectively. In conclusion, our single-vessel synthesis approach for Si-FMIPs proved to be highly effective for the selective determination of captopril in wastewater and synthetic urine samples.


Assuntos
Captopril , Limite de Detecção , Nanopartículas , Águas Residuárias , Captopril/urina , Captopril/análise , Captopril/química , Águas Residuárias/análise , Nanopartículas/química , Polímeros Molecularmente Impressos/química , Corantes Fluorescentes/química , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/urina , Dióxido de Silício/química , Impressão Molecular , Humanos
4.
Biomed Pharmacother ; 176: 116796, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38810397

RESUMO

Spontaneously hypertensive rats (SHR) are characterized by sympathetic hyperactivity and insufficient parasympathetic activity, and their high blood pressure (BP) can be lowered by long-term inhibition of the renin-angiotensin system. The aim of our study was to determine the influence of chronic inhibition of angiotensin converting enzyme (ACE) by captopril on cardiovascular regulation by the sympathetic and parasympathetic nervous system. Implanted radiotelemetric probes or arterial cannulas were used to measure mean arterial pressure (MAP), heart rate (HR), and arterial baroreflex in adult SHR and Wistar-Kyoto (WKY) rats under basal or stress conditions. MAP and the low-frequency component of systolic blood pressure variability (LF-SBPV, marker of sympathetic activity) were greater in SHR than in WKY rats. Under basal conditions chronic captopril treatment reduced both parameters more effectively in SHR, and the same was true during acute restraint stress. HR was similar in control rats of both strains, but WKY rats showed greater heart rate variability (HRV), indicating higher parasympathetic activity. Captopril administration increased HR in both strains, whereas HRV was decreased only in WKY. Chronic captopril treatment improved the impaired baroreflex-HR control in SHR by increasing the sensitivity but not the capacity of vagal arm of arterial baroreflex. Captopril treatment attenuated BP changes elicited by dimethylphenylpiperazinium (DMPP, agonist of nicotinic acetylcholine receptors), especially in SHR, indicating that sympathetic nerve transmission is facilitated by angiotensin II more in hypertensive than in normotensive animals. Thus, chronic ACE inhibition improves baroreflex sensitivity and lowers BP through both central and peripheral attenuation of sympathetic tone.


Assuntos
Inibidores da Enzima Conversora de Angiotensina , Barorreflexo , Pressão Sanguínea , Captopril , Frequência Cardíaca , Sistema Nervoso Simpático , Animais , Masculino , Ratos , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Barorreflexo/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Captopril/farmacologia , Frequência Cardíaca/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Hipertensão/fisiopatologia , Hipertensão/enzimologia , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Sistema Nervoso Simpático/efeitos dos fármacos
6.
Br J Pharmacol ; 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38770714

RESUMO

BACKGROUND AND PURPOSE: This study analyses whether first-line antihypertensive drugs ameliorate the dysbiosis state in hypertension, and to test if this modification contributes to their blood pressure (BP) lowering properties in a genetic model of neurogenic hypertension. EXPERIMENTAL APPROACH: Twenty-week-old male Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) were untreated or treated with captopril, amlodipine or hydrochlorothiazide. A faecal microbiota transplantation (FMT) experiment was also performed by gavage of faecal content from donor SHR-treated groups to SHR recipients for 3 weeks. KEY RESULTS: Faeces from SHR showed gut dysbiosis, characterized by lower acetate- and higher lactate-producing bacteria and lower strict anaerobic bacteria. All three drugs increased the anaerobic bacteria proportion, captopril and amlodipine restored the proportion of acetate-producing bacterial populations to WKY levels, whereas hydrochlorothiazide decreased butyrate-producing bacteria. Captopril and amlodipine decreased gut pathology and permeability and attenuated sympathetic drive in the gut. Both drugs decreased neuroinflammation and oxidative stress in the hypothalamic paraventricular nuclei. Hydrochlorothiazide was unable to reduce neuroinflammation, gut sympathetic tone and gut integrity. FMT from SHR-amlodipine to SHR decreased BP, ameliorated aortic endothelium-dependent relaxation to acetylcholine, lowered NADPH oxidase activity, aortic Th17 infiltration and reduced neuroinflammation, whereas FMT from SHR-hydrochlorothiazide did not have these effects. CONCLUSIONS AND IMPLICATIONS: First-line antihypertensive drugs induced different modifications of gut integrity and gut dysbiosis in SHR, which result in no contribution of microbiota in the BP lowering effects of hydrochlorothiazide, whereas the vasculo-protective effect induced by amlodipine involves gut microbiota reshaping and gut-immune system communication.

7.
Front Endocrinol (Lausanne) ; 15: 1343704, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38586461

RESUMO

Background: To explore the diagnostic accuracy and the optimal cutoff value between the saline infusion test (SIT) and captopril challenge test (CCT) [including the value and suppression of plasma aldosterone concentration (PAC)] for primary aldosteronism (PA) diagnosing. Methods: A total of 318 patients with hypertension were consecutively enrolled, including 126 patients with PA and 192 patients with essential hypertension (EH), in this observational study. The characteristics of patients and laboratory examinations were collected and compared. The comparison between SIT and CCT was carried by drawing the receiver operator characteristic curve (ROC) and calculating the area under the curve (AUC) to explore the diagnostic accuracy and the optimal cutoff value. Results: The average age was 51.59 ± 10.43 in the PA group and 45.72 ± 12.44 in the EH group (p<0.05). The optimal cutoff value was 10.7 ng/dL for post-CCT PAC, 6.8 ng/dL for post-SIT PAC, and 26.9% for suppression of post-CCT PAC. The diagnostic value of post-CCT PAC was the highest with 0.831 for the AUC and 0.552 for the Youden index. The optimal cutoff value for patients who were <50 years old was 11.5 ng/dL for post-CCT PAC and 8.4 ng/dL for post-SIT PAC. The suppression of post-CCT PAC turned to 18.2% for those of age 50 or older. Conclusion: Compared with SIT, CCT had a higher diagnostic value when post-CCT PAC was used as the diagnostic criterion in Chinese people, while the selection of diagnostic thresholds depended on patient age.


Assuntos
Captopril , População do Leste Asiático , Hiperaldosteronismo , Humanos , Adulto , Pessoa de Meia-Idade , Hiperaldosteronismo/diagnóstico , Aldosterona , Hipertensão Essencial/diagnóstico , China/epidemiologia
8.
Int J Mol Sci ; 25(8)2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38674120

RESUMO

Hematopoietic acute radiation syndrome (H-ARS) involves injury to multiple organ systems following total body irradiation (TBI). Our laboratory demonstrated that captopril, an angiotensin-converting enzyme inhibitor, mitigates H-ARS in Göttingen minipigs, with improved survival and hematopoietic recovery, as well as the suppression of acute inflammation. However, the effects of captopril on the gastrointestinal (GI) system after TBI are not well known. We used a Göttingen minipig H-ARS model to investigate captopril's effects on the GI following TBI (60Co 1.79 or 1.80 Gy, 0.42-0.48 Gy/min), with endpoints at 6 or 35 days. The vehicle or captopril (0.96 mg/kg) was administered orally twice daily for 12 days, starting 4 h post-irradiation. Ilea were harvested for histological, protein, and RNA analyses. TBI increased congestion and mucosa erosion and hemorrhage, which were modulated by captopril. GPX-4 and SLC7A11 were downregulated post-irradiation, consistent with ferroptosis at 6 and 35 days post-irradiation in all groups. Interestingly, p21/waf1 increased at 6 days in vehicle-treated but not captopril-treated animals. An RT-qPCR analysis showed that radiation increased the gene expression of inflammatory cytokines IL1B, TNFA, CCL2, IL18, and CXCL8, and the inflammasome component NLRP3. Captopril suppressed radiation-induced IL1B and TNFA. Rectal microbiome analysis showed that 1 day of captopril treatment with radiation decreased overall diversity, with increased Proteobacteria phyla and Escherichia genera. By 6 days, captopril increased the relative abundance of Enterococcus, previously associated with improved H-ARS survival in mice. Our data suggest that captopril mitigates senescence, some inflammation, and microbiome alterations, but not ferroptosis markers in the intestine following TBI.


Assuntos
Síndrome Aguda da Radiação , Captopril , Modelos Animais de Doenças , Ferroptose , Microbioma Gastrointestinal , Inflamação , Porco Miniatura , Irradiação Corporal Total , Animais , Síndrome Aguda da Radiação/tratamento farmacológico , Suínos , Inflamação/patologia , Captopril/farmacologia , Irradiação Corporal Total/efeitos adversos , Ferroptose/efeitos dos fármacos , Microbioma Gastrointestinal/efeitos dos fármacos , Intestinos/microbiologia , Intestinos/patologia , Intestinos/efeitos dos fármacos , Intestinos/efeitos da radiação , Masculino , Inibidores da Enzima Conversora de Angiotensina/farmacologia
9.
Toxicol Appl Pharmacol ; 486: 116946, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38679241

RESUMO

The pathogenesis of attention-deficit/hyperactivity disorder (ADHD) has not been fully elucidated. Gestational hypertension could double the probability of ADHD in the offspring, while the initial bacterial communication between the mother and offspring has been associated with psychiatric disorders. Thus, we hypothesize that antihypertensive treatment during pregnancy may abate the impairments in neurodevelopment of the offspring. To test this hypothesis, we chose Captopril and Labetalol, to apply to pregnant spontaneously hypertensive rat (SHR) dams and examined the outcomes in the male offspring. Our data demonstrated that maternal treatment with Captopril and Labetalol had long-lasting changes in gut microbiota and behavioral alterations, including decreased hyperactivity and increased curiosity, spatial learning and memory in the male offspring. Increased diversity and composition were identified, and some ADHD related bacteria were found to have the same change in the gut microbiota of both the dam and offspring after the treatments. LC-MS/MS and immunohistochemistry assays suggested elevated expression of brain derived neurotrophic factor (BDNF) and dopamine in the prefrontal cortex and striatum of offspring exposed to Captopril/ Labetalol, which may account for the improvement of the offspring's psychiatric functions. Therefore, our results support the beneficial long-term effects of the intervention of gestational hypertension in the prevention of ADHD.


Assuntos
Anti-Hipertensivos , Transtorno do Deficit de Atenção com Hiperatividade , Comportamento Animal , Captopril , Microbioma Gastrointestinal , Efeitos Tardios da Exposição Pré-Natal , Ratos Endogâmicos SHR , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Gravidez , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Transtorno do Deficit de Atenção com Hiperatividade/induzido quimicamente , Feminino , Anti-Hipertensivos/farmacologia , Captopril/farmacologia , Masculino , Ratos , Comportamento Animal/efeitos dos fármacos , Labetalol/farmacologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Hipertensão Induzida pela Gravidez/induzido quimicamente , Dopamina/metabolismo
10.
Eur J Pharmacol ; 973: 176573, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38642669

RESUMO

Parkinson's disease (PD) is characterised by severe movement defects and the degeneration of dopaminergic neurones in the midbrain. The symptoms of PD can be managed with dopamine replacement therapy using L-3, 4-dihydroxyphenylalanine (L-dopa), which is the gold standard therapy for PD. However, long-term treatment with L-dopa can lead to motor complications. The central renin-angiotensin system (RAS) is associated with the development of neurodegenerative diseases in the brain. However, the role of the RAS in dopamine replacement therapy for PD remains unclear. Here, we tested the co-treatment of the angiotensin-converting enzyme inhibitor (ACEI) with L-dopa altered L-dopa-induced dyskinesia (LID) in a 6-hydroxydopamine (6-OHDA)-lesioned mouse model of PD. Perindopril, captopril, and enalapril were used as ACEIs. The co-treatment of ACEI with L-dopa significantly decreased LID development in 6-OHDA-lesioned mice. In addition, the astrocyte and microglial transcripts involving Ccl2, C3, Cd44, and Iigp1 were reduced by co-treatment with ACEI and L-dopa in the 6-OHDA-lesioned striatum. In conclusion, co-treatment with ACEIs and L-dopa, such as perindopril, captopril, and enalapril, may mitigate the severity of L-DOPA-induced dyskinesia in a mouse model of PD.


Assuntos
Inibidores da Enzima Conversora de Angiotensina , Modelos Animais de Doenças , Discinesia Induzida por Medicamentos , Levodopa , Oxidopamina , Animais , Masculino , Camundongos , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Antiparkinsonianos/farmacologia , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Captopril/farmacologia , Captopril/uso terapêutico , Discinesia Induzida por Medicamentos/tratamento farmacológico , Discinesia Induzida por Medicamentos/prevenção & controle , Enalapril/farmacologia , Enalapril/uso terapêutico , Levodopa/toxicidade , Camundongos Endogâmicos C57BL , Microglia/efeitos dos fármacos , Microglia/metabolismo , Doença de Parkinson/tratamento farmacológico , Perindopril/farmacologia , Perindopril/uso terapêutico
11.
Hypertens Res ; 47(5): 1362-1371, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38454147

RESUMO

The measurement evolution enabled more accurate evaluation of aldosterone production in hypertensive patients. However, the cut-off values for novel assays have been not sufficiently validated. The present study was undertaken to validate the novel chemiluminescent enzyme immunoassay for aldosterone in conjunction with other methods. Moreover, we also aimed to establish a new cut-off value for primary aldosteronism in the captopril challenge test using the novel assay. First, we collected 390 plasma samples, in which aldosterone levels measured using liquid chromatography-mass spectrometry ranged between 0.18 and 1346 ng/dL. The novel chemiluminescent enzyme immunoassay showed identical correlation of plasma aldosterone with liquid chromatography-mass spectrometry, in contrast to conventional radioimmunoassay. Further, we enrolled 299 and 39 patients with primary aldosteronism and essential hypertension, respectively. Plasma aldosterone concentrations measured using the novel assay were lower than those measured by radioimmunoassay, which resulted in decreased aldosterone-to-renin ratios. Subsequently, positive results of the captopril challenge test based on radioimmunoassay turned into "negative" based on the novel assay in 45% patients with primary aldosteronism, using the conventional cut-off value (aldosterone-to-renin activity ratio > 20 ng/dL per ng/mL/h). Receiver operating characteristic curve analysis demonstrated that aldosterone-to-renin activity ratios > 8.2 ng/dL per ng/mL/h in the novel assay was compatible with the conventional diagnosis (sensitivity, 0.874; specificity, 0.980). Our study indicates the great measurement accuracy of the novel chemiluminescent enzyme immunoassay for aldosterone, and the importance of measurement-adjusted cut-offs in the diagnosis of primary aldosteronism.


Assuntos
Aldosterona , Captopril , Hiperaldosteronismo , Medições Luminescentes , Humanos , Hiperaldosteronismo/diagnóstico , Hiperaldosteronismo/sangue , Masculino , Feminino , Pessoa de Meia-Idade , Aldosterona/sangue , Estudos Retrospectivos , Adulto , Idoso , Medições Luminescentes/métodos , Técnicas Imunoenzimáticas/métodos , Hipertensão/sangue , Hipertensão/diagnóstico , Renina/sangue , Estudos de Coortes , Radioimunoensaio
12.
J Orthop Surg Res ; 19(1): 147, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38373964

RESUMO

PURPOSE: Patients are typically diagnosed with both hypertension and fibrosarcoma. Medical oncologists must prescribe suitable anti-hypertensive medications while considering anti-tumor drugs. Recently, immunotherapy has become prominent in cancer treatment. Nonetheless, it is unknown what role anti-hypertensive medications will play in immunotherapy. METHODS: We examined the effects of six first-line anti-hypertensive medications on programmed cell death protein 1 antibody (PD1ab) in tumor treatment using a mouse model of subcutaneous fibrosarcoma. The drugs examined were verapamil, losartan, furosemide, spironolactone, captopril, and hydrochlorothiazide (HCTZ). The infiltration of CD8+ T cells was examined by immunohistochemistry. Additionally, several in vitro and in vivo assays were used to study the effects of HCTZ on human fibrosarcoma cancer cells to explore its mechanism. RESULTS: Verapamil suppressed tumor growth and showed an improved effect on the tumor inhibition of PD1ab. Captopril did not affect tumor growth but brought an unexpected benefit to PD1ab treatment. In contrast, spironolactone and furosemide showed no effect on tumor growth but had an offset effect on the PD1ab therapy. Consequently, the survival time of mice was also significantly reduced. Notably, losartan and HCTZ, especially HCTZ, promoted tumor growth and weakened the effect of PD1ab treatment. Consistent results were observed in vivo and in vitro using the human fibrosarcoma cell line HT1080. We determined that the Solute Carrier Family 12 Member 3 (SLC12A3), a known target of HCTZ, may be the principal factor underlying its effect-enhancing properties through mechanism studies employing The Cancer Genome Atlas (TCGA) data and in vivo and in vitro assays. CONCLUSION: Verapamil and captopril potentiated the anti-tumor effect of PD1ab, whereas spironolactone and furosemide weakened the effect of PD1ab on tumor inhibition. Alarmingly, losartan and HCTZ promoted tumor growth and impaired the effect of PD1ab. Furthermore, we preliminarily found that HCTZ may promote tumor progression through SLC12A3. Based on this study, futher mechanism researches and clinical trials should be conducted in the future.


Assuntos
Fibrossarcoma , Hipertensão , Humanos , Anti-Hipertensivos/uso terapêutico , Losartan/farmacologia , Losartan/uso terapêutico , Captopril/farmacologia , Captopril/uso terapêutico , Espironolactona/uso terapêutico , Furosemida/uso terapêutico , Linfócitos T CD8-Positivos , Hipertensão/tratamento farmacológico , Hidroclorotiazida/uso terapêutico , Quimioterapia Combinada , Verapamil/farmacologia , Verapamil/uso terapêutico , Fibrossarcoma/tratamento farmacológico , Membro 3 da Família 12 de Carreador de Soluto
13.
J Fluoresc ; 2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38329605

RESUMO

In this study, a novel dinuclear lanthanide complex, denoted as [Ho2(L)2(acac)2(CH3OH)2]·CH3OH (1) (where H2L is 2-[((4-methyl)-2-(carboxyl)-imino)]methyl]-8-hydroxyquinoline, and Hacac is acetylacetonate), was successfully synthesized and characterized using single-crystal and elemental analysis, with the auxiliary ligand ß-diketonate and the 8-hydroxyquinoline Schiff base derivative serving as the foundation. Through ligand-to-metal charge transfer, Compound 1 demonstrated remarkable green fluorescence properties, showcasing potential applications in green fluorescence materials and fluorescence sensing. Additionally, Hyaluronic Acid (HA)/Carboxymethyl Chitosan (CMCS) hydrogels were synthesized through a chemical method. Utilizing captopril as a drug model, a novel metal gel granule of captopril was developed and assessed for its inhibitory activity against glioma cells. Molecular docking simulations revealed that only the methanol group in the Ho complex could contribute a polar atom for the formation of binding interactions.

14.
Endocr Connect ; 13(3)2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38180077

RESUMO

Primary aldosteronism (PA) is the most common cause of endocrine hypertension and is often underdiagnosed. This condition is associated with increased cardiovascular morbidity and mortality in comparison to age and blood pressure matched individuals with essential hypertension (EH). The diagnostic pathway for PA consists of three phases: screening, confirmatory testing, and subtyping. The lack of specificity in the screening step, which relies on the aldosterone to renin ratio, necessitates confirmatory testing. The Endocrine Society's clinical practice guideline suggests four confirmatory tests, including the fludrocortisone suppression test (FST), saline suppression test (SST), captopril challenge test (CCT), and oral sodium loading test (SLT). There is no universally accepted choice of confirmatory test, with practices varying among centers. The SST and FST are commonly used, but they can be resource-intensive, carry risks such as volume overload or hypokalemia, and are contraindicated in severe/uncontrolled HTN as well as in cardiac and renal impairment. In contrast, CCT is a safe and inexpensive alternative that can be performed in an outpatient setting and can be applied when other tests are contraindicated. Despite its simplicity and convenience, the variability in captopril dose, testing posture, and diagnostic threshold limit its widespread use. This narrative review evaluates the diagnostic accuracy of the CCT across different populations, addresses controversies in its usage, and proposes recommendations for its use in the diagnosis of PA. Furthermore, suggestions for future research aimed at promoting the wider utilization of the CCT as a simpler, safer, and more cost-effective diagnostic test are discussed.

15.
Development ; 151(3)2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38284547

RESUMO

The renin-angiotensin-aldosterone system (RAAS) plays a well-characterized role regulating blood pressure in mammals. Pharmacological and genetic manipulation of the RAAS has been shown to extend lifespan in Caenorhabditis elegans, Drosophila and rodents, but its mechanism is not well defined. Here, we investigate the angiotensin-converting enzyme (ACE) inhibitor drug captopril, which extends lifespan in worms and mice. To investigate the mechanism, we performed a forward genetic screen for captopril-hypersensitive mutants. We identified a missense mutation that causes a partial loss of function of the daf-2 receptor tyrosine kinase gene, a powerful regulator of aging. The homologous mutation in the human insulin receptor causes Donohue syndrome, establishing these mutant worms as an invertebrate model of this disease. Captopril functions in C. elegans by inhibiting ACN-1, the worm homolog of ACE. Reducing the activity of acn-1 via captopril or RNA interference promoted dauer larvae formation, suggesting that acn-1 is a daf gene. Captopril-mediated lifespan extension was abrogated by daf-16(lf) and daf-12(lf) mutations. Our results indicate that captopril and acn-1 influence lifespan by modulating dauer formation pathways. We speculate that this represents a conserved mechanism of lifespan control.


Assuntos
Proteínas de Caenorhabditis elegans , Captopril , Animais , Humanos , Camundongos , Captopril/farmacologia , Captopril/metabolismo , Caenorhabditis elegans/metabolismo , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Inibidores da Enzima Conversora de Angiotensina/metabolismo , Proteínas de Caenorhabditis elegans/metabolismo , Envelhecimento , Longevidade/fisiologia , Receptor de Insulina/metabolismo , Mutação/genética , Mamíferos/metabolismo
16.
BMC Chem ; 18(1): 15, 2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38254234

RESUMO

Preserving the environment, reducing the amount of waste resulting from chemical trials, and reducing the amount of energy consumed have currently become a pivotal global trend. An analytical quality by design (AQbD) based eco-friendly TLC-densitometric method was implemented for quantifying two antihypertensive agents, captopril (CPL) and hydrochlorothiazide (HCZ), along with their impurities; captopril disulphide (CDS), chlorothiazide (CTZ) and salamide (SMD). The analytical target profile (ATP) was first identified, followed by selecting the critical analytical attributes (CAAs), such as retardation factors and resolution between the separated peaks. Critical method parameters (CMPs) that may have a crucial influence on CAAs were identified and emanated through the quality risk assessment phase. A literature survey-based preliminary studies were performed, followed by optimization of the selected CMPs through a custom experimental design to attain the highest resolution with optimum retardation factors. Moreover, method robustness was also tested by testing the design space. Complete separation of the drugs and their impurities was achieved using ethyl acetate: glacial acetic acid (6: 0.6, v/v) as a developing system applied to a 12 cm length TLC plate at room temperature with UV scanning at 215 nm. Calibration graphs were found to be linear in the ranges of (0.70-6.00), (0.10-2.00), (0.20-1.00), (0.07-1.50) and (0.05-1.00) µg/band corresponding to CPL, HCZ, CDS, CTZ, and SMD, respectively. Four different green metric tools were used to evaluate the greenness profile of the proposed method, and results showed that it is greener than the reported HPLC method. Method whiteness assessment was also conducted. Moreover, the method performance was evaluated following the ICH guidelines, and the outcomes fell within the acceptable limits. The developed method could be approved for routine assay of the cited components in their pharmaceutical formulations and bulk powder without interference from the reported impurities. The issue of concern is saving money, especially in developing countries.

17.
J Formos Med Assoc ; 123 Suppl 2: S104-S113, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37173227

RESUMO

Confirmatory tests for diagnosis of primary aldosteronism (PA) play an important role in sparing patients with a false-positive aldosterone-to-renin ratio (ARR) screening test from undergoing invasive subtyping procedures. We recommend that patients with a positive ARR test should undergo at least one confirmatory test to confirm or exclude the diagnosis of PA before directly proceeding to subtype studies, except for patients with significant PA phenotypes, including spontaneous hypokalemia, plasma aldosterone concentration >20 ng/dL plus plasma renin activity below a detectable level. Although a gold standard confirmatory test has not been identified, we recommend that saline infusion test and captopril challenge test, which were widely used in Taiwan. Patients with PA have been reported to have a higher prevalence of concurrent autonomous cortisol secretion (ACS). ACS is a biochemical condition of mild cortisol overproduction from adrenal lesions, but without the typical clinical features of overt Cushing's syndrome. Concurrent ACS may result in incorrect interpretation of adrenal venous sampling (AVS) and may lead to adrenal insufficiency after adrenalectomy. We recommend screening for ACS in patients with PA scheduled for AVS examinations as well as for adrenalectomy. We recommend the 1-mg overnight dexamethasone suppression test as screening method to detect ACS.


Assuntos
Hiperaldosteronismo , Hipertensão , Humanos , Aldosterona , Hiperaldosteronismo/diagnóstico , Renina , Hidrocortisona , Captopril
18.
Int J Biol Macromol ; 255: 128087, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37979743

RESUMO

Captopril (CTP) is an oral drug widely used to treat high blood pressure and congestive heart failure. In this study, CTP-incorporated biomaterials for antihypertensive therapy were synthesized from chitosan, carboxymethyl cellulose, and plasticizers. The physicochemical properties of the prepared biomaterials were characterized using FE-SEM, FT-IR analysis, and physical properties. CTP release experiments were carried out in buffer solutions at various pH values and temperatures. Results indicated that above 99.0 % of CTP was released within 180 min. Optimization of the experimental conditions for CTP release was analyzed by using response surface methodology (RSM). Results of CTP release through artificial skin indicated that CTP was continuously released above 95.0 % from the prepared biomaterials for 36.0 h. The CTP release mechanisms into a buffer and through artificial skin followed pseudo-Fickian diffusion mechanism and non-Fickian diffusion mechanisms, respectively. Moreover, angiotensin-converting enzyme (ACE) inhibition (related to cardiovascular disease) via the released CTP clearly reveals that the prepared biomaterials have a high potential as a transdermal drug delivery agent in antihypertensive therapy.


Assuntos
Captopril , Quitosana , Captopril/química , Captopril/uso terapêutico , Anti-Hipertensivos/química , Quitosana/química , Carboximetilcelulose Sódica/química , Liberação Controlada de Fármacos , Materiais Biocompatíveis , Espectroscopia de Infravermelho com Transformada de Fourier , Portadores de Fármacos/química
19.
Pediatr Cardiol ; 45(2): 394-400, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38153545

RESUMO

Hypertension after cardiothoracic surgery is common, often requiring pharmacologic management. The recommended first-line antihypertensives in pediatrics are angiotensin converting enzyme inhibitors. Captopril and enalapril are approved for infants and children; however, lisinopril is only approved for > 7 years of age. This study evaluated safety and efficacy of converting from captopril to lisinopril in patients utilizing a pre-defined conversion of 3 mg captopril to 1 mg lisinopril. This was a single center, retrospective study including patients less than 7 years of age admitted for cardiothoracic surgery who received both captopril and lisinopril from 01/01/2017 to 06/01/2022.The primary outcome was mean change in systolic blood pressure (SBP) from baseline for 72 h after conversion of captopril to lisinopril. A total of 99 patients were enrolled. There was a significant decrease in mean SBP (99.12 mmHg vs 94.86 mmHg; p = 0.007) with no difference in DBP (59.23 mmHg vs 61.95 mmHg; p = 0.07) after conversion to lisinopril. Of the 99 patients who were transitioned to lisinopril, 79 (80%) had controlled SBP, 20 (20%) remained hypertensive, 13 (13%) received an increase in their lisinopril dose, and 2 (2%) required an additional antihypertensive agent. There was a low overall rate of AKI (3%) and hyperkalemia (4%) respectively. This study demonstrates that utilizing lisinopril with a conversion rate of 3 mg of captopril to 1 mg of lisinopril was safe and effective for controlling hypertension in pediatric patients following cardiothoracic surgery.


Assuntos
Hipertensão , Lisinopril , Humanos , Criança , Lisinopril/uso terapêutico , Lisinopril/farmacologia , Captopril/uso terapêutico , Captopril/farmacologia , Estudos Retrospectivos , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Hipertensão/tratamento farmacológico , Anti-Hipertensivos/uso terapêutico , Anti-Hipertensivos/farmacologia , Enalapril , Pressão Sanguínea
20.
Arch Esp Urol ; 76(7): 532-537, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37867339

RESUMO

OBJECTIVE: This study aimed to investigate the clinical value of the combination detection of captopril renal scintigraphy (CRS) and plasma renin activity (PRA) in the diagnosis of renal hypertension (RHR). METHODS: Retrospective analysis was conducted on the clinical data of 163 patients with suspected RHR admitted to our hospital from March 2019 to March 2021, and all patients underwent blood pressure, CRS and digital subtraction angiography (DSA). The patients were divided into the positive group (n = 100) and the negative group (n = 63) in accordance with the results of DSA examination. PRA, angiotensin II and aldosterone levels of the two groups were detected and compared. The receiver operating characteristic curve was used to analyse the CRS, PRA and combined diagnostic performance. RESULTS: The uptake ratio value after captopril intervention in the positive group was 36.71% ± 8.79%, which was significantly lower than that in the negative group (56.79% ± 10.09%, p < 0.05). The serum PRA level of the positive group was 4.70 ± 1.67 ng/mLꞏh, which was distinctly higher than that of the negative group (2.12 ± 1.03 ng/mLꞏh, p < 0.05). The sensitivity and Youden index under the combination detection (area under the curve (AUC) = 0.956, p < 0.001) were all higher than those under single detection. CONCLUSION: The combined detection of PRA and CRS can provide considerable evidence for the early diagnosis and treatment of RHR, which has a certain clinical value.


Assuntos
Captopril , Hipertensão Renal , Renina , Humanos , Pressão Sanguínea , Captopril/uso terapêutico , Hipertensão Renal/diagnóstico , Cintilografia , Renina/sangue , Estudos Retrospectivos
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