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1.
Zool Res ; 42(5): 633-636, 2021 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-34423606

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiologic agent responsible for the global coronavirus disease 2019 (COVID-19) pandemic. Numerous studies have demonstrated that cardiovascular disease may affect COVID-19 progression. In the present study, we investigated the effect of hypertension on viral replication and COVID-19 progression using a hypertensive mouse model infected with SARS-CoV-2. Results revealed that SARS-CoV-2 replication was delayed in hypertensive mouse lungs. In contrast, SARS-CoV-2 replication in hypertensive mice treated with the antihypertensive drug captopril demonstrated similar virus replication as SARS-CoV-2-infected normotensive mice. Furthermore, antihypertensive treatment alleviated lung inflammation induced by SARS-CoV-2 replication (interleukin (IL)-1ß up-regulation and increased immune cell infiltration). No differences in lung inflammation were observed between the SARS-CoV-2-infected normotensive mice and hypertensive mice. Our findings suggest that captopril treatment may alleviate COVID-19 progression but not affect viral replication.


Assuntos
Anti-Hipertensivos/uso terapêutico , COVID-19/complicações , Captopril/uso terapêutico , Hipertensão/complicações , Pneumopatias/tratamento farmacológico , SARS-CoV-2 , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Animais , Anti-Hipertensivos/farmacologia , Captopril/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Inflamação/complicações , Inflamação/tratamento farmacológico , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Pneumopatias/etiologia , Pneumopatias/virologia , Camundongos , Replicação Viral/efeitos dos fármacos
2.
Chem Biol Interact ; 347: 109604, 2021 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-34352275

RESUMO

Angiotensin-converting enzyme (ACE, EC 3.4.15.1) synthesized by endothelial cells and responsible for the regulation of blood pressure was purified from the bovine lung with affinity chromatography method. The purification rate of the ACE of the bovine lung was calculated as 1748- fold. Optimum pH and optimum temperature for the purified ACE were found to be 7.6 and 35-40 °C, respectively. The purity and molecular weight of the ACE were designated with SDS-PAGE. The ACE was found to have three subunits with molecular weights of 57 kDa, 66 kDa, and 190 kDa. Then, the total molecular weight of the ACE was designated as 303 kDa with gel filtration chromatography. The effects of ACE inhibitors captopril, fosinopril, lisinopril, and beta-blockers propranolol, atenolol, and diuretic triamterene on ACE activity were studied. ACE inhibitors lisinopril, captopril, fosinopril, and diuretic triamterene demonstrated an inhibition effect on ACE activity. Beta-blockers indicated no effect on ACE. IC50 values of captopril, fosinopril, lisinopril, and triamterene from the graphical equation were calculated as 0.835 nM, 1.159 µM, 4.085 nM, and 227 µM, respectively. The inhibition type and Ki values of these compounds were determined from Lineweaver-Burk plots. Captopril, fosinopril, lisinopril, and triamterene demonstrated a non-competitive inhibition effect on ACE activity. Ki constants were found as 1.057 nM, 1.675 µM, 6.449 nM, and 419.5 µM, respectively. Captopril indicated the highest inhibitor effect with an IC50 value of 0.835 nM.


Assuntos
Peptidil Dipeptidase A/isolamento & purificação , Inibidores da Enzima Conversora de Angiotensina/química , Animais , Captopril/química , Bovinos , Cromatografia de Afinidade , Fosinopril/química , Concentração de Íons de Hidrogênio , Cinética , Lisinopril/química , Pulmão/química , Peptidil Dipeptidase A/química , Estabilidade Proteica , Temperatura , Triantereno/química
3.
Nutrients ; 13(7)2021 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-34371955

RESUMO

Despite the well-established role of quinoa protein as the source of antihypertensive peptides through in vitro enzymolysis, there is little evidence supporting the in vivo antihypertensive effect of intact quinoa protein. In this study, in vivo study on spontaneously hypertensive rats (SHRs) was conducted by administering quinoa protein for five weeks. Gastrointestinal content identification indicated that many promising precursors of bioactive peptides were released from quinoa protein under gastrointestinal processing. Quinoa protein administration on SHRs resulted in a significant decrease in blood pressure, a significant increase in alpha diversity, and microbial structure alternation towards that in non-hypertension rats. Furthermore, blood pressure was highly negatively correlated with the elevated abundance of genera in quinoa protein-treated SHRs, such as Turicibacter and Allobaculum. Interestingly, the fecal microbiota in quinoa protein-treated SHRs shared more features in the composition of genera with non-hypertension rats than that of the captopril-treated group. These results indicate that quinoa protein may serve as a potential candidate to lower blood pressure and ameliorate hypertension-related gut dysbiosis.


Assuntos
Pressão Sanguínea , Captopril/administração & dosagem , Chenopodium quinoa , Proteínas na Dieta/administração & dosagem , Microbioma Gastrointestinal , Hipertensão/fisiopatologia , Proteínas de Plantas/administração & dosagem , Animais , Anti-Hipertensivos/administração & dosagem , Bactérias/classificação , Bactérias/isolamento & purificação , Proteínas na Dieta/metabolismo , Digestão , Fezes/microbiologia , Trato Gastrointestinal/metabolismo , Trato Gastrointestinal/microbiologia , Hipertensão/tratamento farmacológico , Masculino , Peptídeos/análise , Proteínas de Plantas/metabolismo , Ratos , Ratos Endogâmicos SHR
4.
Int J Mol Sci ; 22(15)2021 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-34360587

RESUMO

In the present study, we analyzed the activity of several aminopeptidases (angiotensinases) involved in the metabolism of various angiotensin peptides, in pituitary and adrenal glands of untreated Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) or treated with the antihypertensive drugs captopril and propranolol or with the L-Arginine hypertensive analogue L-NG-Nitroarginine Methyl Ester (L-NAME). Intra- and inter-gland correlations between angiotensinase activities were also calculated. Membrane-bound alanyl-, cystinyl-, and glutamyl-aminopeptidase activities were determined fluorometrically using aminoacyl-ß-naphthylamide as substrates. Depending on the type of angiotensinase analyzed, the results reflect a complex picture showing substantial differences between glands, strains, and treatments. Alanyl-aminopeptidase responsible for the metabolism of Ang III to Ang IV appears to be the most active angiotensinase in both pituitary and adrenals of WKY and particularly in SHR. Independently of treatment, most positive correlations are observed in the pituitary gland of WKY whereas such positive correlations are predominant in adrenals of SHR. Negative inter-gland correlations were observed in control SHR and L-NAME treated WKY. Positive inter-gland correlations were observed in captopril-treated SHR and propranolol-treated WKY. These results may reflect additional mechanisms for increasing or decreasing systolic blood pressure in WKY or SHR.


Assuntos
Glândulas Suprarrenais/metabolismo , Anti-Hipertensivos/farmacologia , Endopeptidases/metabolismo , Hipertensão/metabolismo , Hipotensão/metabolismo , NG-Nitroarginina Metil Éster/farmacologia , Hipófise/metabolismo , Glândulas Suprarrenais/efeitos dos fármacos , Animais , Captopril/farmacologia , Endopeptidases/genética , Inibidores Enzimáticos/farmacologia , Regulação Enzimológica da Expressão Gênica , Hipertensão/tratamento farmacológico , Hipertensão/patologia , Hipotensão/tratamento farmacológico , Hipotensão/patologia , Masculino , Hipófise/efeitos dos fármacos , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY
5.
Langmuir ; 37(30): 9170-9178, 2021 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-34292730

RESUMO

The peptide angiotensin-converting enzyme inhibitors captopril and lisinopril are unexpectedly shown to exhibit critical aggregation concentration (CAC) behavior through measurements of surface tension, electrical conductivity, and dye probe fluorescence. These three measurements provide similar values for the CAC, and there is also evidence from circular dichroism spectroscopy for a possible conformational change in the peptides at the same concentration. Cryogenic transmission electron microscopy indicates the formation of micelle-like aggregates above the CAC, which can thus be considered a critical micelle concentration, and the formation of aggregates with a hydrodynamic radius of ∼6-7 nm is also evidenced by dynamic light scattering. We also used synchrotron radiation X-ray diffraction to determine the single-crystal structure of captopril and lisinopril. Our results improve the accuracy of previous data reported in the literature, obtained using conventional X-ray sources. We also studied the structure of aqueous solutions containing captopril or lisinopril at high concentrations. The aggregation may be driven by intermolecular interactions between the proline moiety of captopril molecules or between the phenylalanine moiety of lisinopril molecules.


Assuntos
Captopril , Lisinopril , Inibidores da Enzima Conversora de Angiotensina
6.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 50(2): 179-186, 2021 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-34137232

RESUMO

To investigate the effect of captopril on the dentin bonding durability of self-etch adhesive. Different concentrations of captopril ethanol solutions or captopril ethanol/water solutions were prepared to pretreat dentin as primer for the self-etch adhesives. The surface morphology of the dentin was observed with scanning electron microscopy (SEM). Based on the morphology analysis, the pretreatment condition was selected and two self-etch adhesives were employed to evaluate the improvement effect of the captopril pretreatment on the dentin bonding durability. : SEM showed that the pretreatment of captopril ethanol solutions and captopril ethanol/water solutions were able to remove the smear lay and partially expose collagen matrix. According to the SEM results, the pretreating condition of captopril ethanol/water solution with the pretreating time of was selected for further dentin bonding study. For Clearfil SEBOND system, the immediate bonding strength increased from to  (<0.05). After one-year aging, the bonding strength of the control group decreased markedly [(22.90±6.82) MPa, <0.05]; while the bonding strength of the captopril pretreated group kept steadily >0.05]. For Clearfil S BOND system, there was no significant difference in the immediate bonding strength between the experimental group [(4.07) MPa] and the control group[(4.11) MPa]. But after one-year aging, the bonding strength of the experimental group was higher than that of the control group <0.05]. : The pretreatment with captopril ethanol/water solution increases the dentin bonding strength of the self-etch adhesive systems and also improves the bonding durability.


Assuntos
Colagem Dentária , Adesivos Dentinários , Adesivos , Captopril , Dentina , Teste de Materiais , Microscopia Eletrônica de Varredura , Cimentos de Resina
7.
Biomed Pharmacother ; 139: 111670, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33945910

RESUMO

Cisplatin (Cis) is an effective cancer therapy commonly employed in many therapeutic regimens. However, treatment regimens that contain either a high dose or cumulative doses of Cis could trigger liver damage. A unique study demonstrated that captopril (Cap) protects against Cis-induced liver toxicity, but only some liver function enzymes and some antioxidant enzymes were investigated in that study. Our study aims to elucidate the protective mechanism of Cap against Cis liver toxicity. Acute liver toxicity was induced in rats by injecting a single Cis dose (7.5 mg/kg) in three groups (n = 6). Two groups were pre-treated with low (50 mg/kg) and high (100 mg/kg) Cap doses for one week before Cis injection, and the third group was injected with Cis only. The high Cap dose significantly improved liver function markers (ALT, AST, and ALP) and hepatic tissue pathology. The low Cap dose significantly improved ALP and, to a lesser extent, hepatic tissue pathology. Both Cap doses significantly decreased liver contents of MDA, IL-1ß, and cleaved caspase-3; and liver protein expression of TNF-α, Bax, and caspase-3. The high Cap dose significantly increased liver contents of GSH, GPx, CAT, and SOD, and the liver protein expression of Bcl2. Moreover, only the high Cap dose significantly decreased liver IL-6 content and cytochrome C protein expression. Cap did not inhibit the antitumor impact of Cis against HCT116 cancer cells. Therefore, Cap restricts Cis-induced liver toxicity by reducing inflammation and apoptosis and augmenting the antioxidant system.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/farmacologia , Anti-Inflamatórios/farmacologia , Apoptose/efeitos dos fármacos , Captopril/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Animais , Antineoplásicos , Antioxidantes/farmacologia , Caspase 3/efeitos dos fármacos , Linhagem Celular Tumoral , Cisplatino , Citocromos c , Regulação para Baixo/efeitos dos fármacos , Humanos , Testes de Função Hepática , Masculino , Ratos , Ratos Wistar , Proteína X Associada a bcl-2
8.
Clin Exp Hypertens ; 43(6): 536-549, 2021 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-33870805

RESUMO

Background: Left ventricular hypertrophy (LVH) is an endpoint of hypertensive cardiac alterations. Renin-angiotensin-aldosterone system (RAAS) blockers are among the most effective on LVH regression. Physical exercise combined to antihypertensive drug contributes to arterial pressure (AP) control and LVH prevention. We evaluated the effects of physical exercise combined to captopril or losartan during eight weeks for spontaneously hypertensive rats (SHR) on some cardiac parameters.Methods: SHR (n=5-6 per group) were sedentary or trained 5 days a week in treadmill during 8 weeks; and they were treated with daily oral captopril (12.5, 25, or 50mg/kg), losartan (2.5, 5, or 10mg/kg), or vehicle. At the end, it was obtained systolic AP (SAP), electrocardiogram (ECG), and hearts metalloproteinase 2 (MMP-2) activity and histology.Results: Captopril 25 and 50 mg/kg, and losartan 10 mg/kg lowered SAP of sedentary and trained SHR. Losartan 5 mg/kg combined with physical exercise also lowered SAP. Combined with exercise, captopril 50 mg/kg lowered 13.6% of QT interval, 14.2% of QTc interval, and 22.8% of Tpeak-Tend compared to sedentary SHR. Losartan 5 and 10mg/kg lowered QT interval of sedentary and trained SHR. Losartan 2.5, 5 and 10mg/kg combined with physical exercise lowered respectively 25.4%, 24.8%, and 31.8% of MMP-2 activity. Losartan (10mg/kg) combined with exercise reduced cardiomyocyte diameter.Conclusion: These data support the hypothesis of physical exercise combined with RAAS blockers could improve the benefits on hypertensive LVH treatment.


Assuntos
Hipertensão , Hipertrofia Ventricular Esquerda , Losartan , Animais , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Captopril/farmacologia , Hipertensão/tratamento farmacológico , Hipertrofia Ventricular Esquerda/prevenção & controle , Losartan/farmacologia , Metaloproteinase 2 da Matriz/farmacologia , Ratos , Ratos Endogâmicos SHR
9.
Clin Sci (Lond) ; 135(8): 1009-1014, 2021 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-33881142

RESUMO

Angiotensin-converting enzyme 2 (ACE2) is the leading player of the protective renin-angiotensin system (RAS) pathway but also the entry receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). RAS inhibitors seemed to interfere with the ACE2 receptor, and their safety was addressed in COVID-19 patients. Pedrosa et al. (Clin. Sci. (Lond.) (2021), 135, 465-481) showed in rats that captopril and candesartan up-regulated ACE2 expression and the protective RAS pathway in lung tissue. In culture of pneumocytes, the captopril/candesartan-induced ACE2 up-regulation was associated with inhibition of ADAM17 activity, counterbalancing increased ACE2 expression, which was associated with reduced SARS-CoV-2 spike protein entry. If confirmed in humans, these results could become the pathophysiological background for justifying RAS inhibitors as cornerstone cardiovascular protectives even during COVID-19 pandemic.


Assuntos
Inibidores da Enzima Conversora de Angiotensina , COVID-19 , Antagonistas de Receptores de Angiotensina , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Animais , Benzimidazóis , Compostos de Bifenilo , Captopril/farmacologia , Humanos , Pandemias , Peptidil Dipeptidase A/metabolismo , Ratos , Sistema Renina-Angiotensina , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Tetrazóis
10.
Biomacromolecules ; 22(5): 1910-1920, 2021 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-33844512

RESUMO

Misfolding proteins could form oligomers or amyloid fibers, which can cause a variety of amyloid-associated diseases. Thus, the inhibition of protein misfolding and fibrillation is a promising way to prevent and treat these diseases. Captopril (CAP) is an angiotensin-converting enzyme inhibitor (ACEI) that is widely used to treat diseases such as hypertension and heart failure. In this study, we found that CAP inhibits human lysozyme (HL) fibrillation through the combination techniques of biophysics and biochemistry. The data obtained by thioflavin-T (ThT) and Congo red (CR) assays showed that CAP hindered the aggregation of HL amyloid fibrils by reducing the ß-sheet structure of HL amyloid, with an IC50 value of 34.75 ± 1.23 µM. Meanwhile, the particle size of HL amyloid decreased sharply in a concentration-dependent approach after CAP treatment. According to the visualization of atomic force microscopy (AFM) and transmission electron microscopy (TEM), we verified that in the presence of CAP, the needle-like fibers of HL amyloid were significantly reduced. In addition, CAP incubation dramatically improved the cell survival rate exposed to HL fibers. Our studies also revealed that CAP could form hydrogen bonds with amino acid residues of Glu 35 and Ala 108 in the binding pocket of HL, which help in maintaining the α-helical structure of HL and then prevent the formation of amyloid fibrillation. It can be concluded that CAP has antiamyloidogenic activity and a protective effect on HL amyloid cytotoxicity.


Assuntos
Amiloide , Muramidase , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Captopril/farmacologia , Humanos , Análise Espectral
11.
Horm Behav ; 130: 104952, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33647281

RESUMO

Spontaneously hypertensive rats (SHRs) ingest more NaCl than normotensive strains. Here we investigated NaCl intake and taste reactivity in adult male SHRs and normotensive Holtzman rats treated or not with AT1 receptor antagonist centrally in euhydrated condition and after fluid depletion. Taste reactivity was measured by the number of orofacial expressions to intra-oral infusions of 0.3 M NaCl. In euhydrated condition, intra-oral infusions of 0.3 M NaCl produced greater number of hedonic responses in SHRs than in normotensive rats, without differences in the number of aversive responses. Compared to euhydrated condition, the treatment with the diuretic furosemide + low dose of captopril (angiotensin converting enzyme blocker) increased the number of hedonic and reduced the number of aversive responses to intra-oral NaCl in normotensive rats, without changing the number of hedonic or aversive responses in SHRs. Losartan (AT1 receptor antagonist, 100 ng/1 µl) injected intracerebroventricularly in SHRs abolished 0.3 M NaCl intake induced by water deprivation + partial rehydration, whereas only transiently (first 30 min of the 60 min test) reduced hedonic responses, without changes in aversive responses to intra-oral NaCl. Losartan intracerebroventricularly also only transiently (first 30 min) reduced the number of hedonic responses to intra-oral NaCl in euhydrated SHRs. The results suggest that NaCl palatability is increased and independent from body fluid balance in SHRs. The results also suggest that central AT1 receptors are part of the mechanisms activated to increase NaCl intake and palatability in SHRs. A partial dissociation between NaCl intake and palatability in SHRs is also suggested.


Assuntos
Captopril , Sódio , Animais , Captopril/farmacologia , Furosemida/farmacologia , Losartan/farmacologia , Masculino , Ratos , Ratos Endogâmicos SHR
12.
Nutrients ; 13(2)2021 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-33672674

RESUMO

Wine lees (WL) are by-products generated in the winemaking process. The aim of this study was to investigate the angiotensin-converting enzyme inhibitory (ACEi) activity, and the blood pressure (BP) lowering effect of WL from individual grape varieties. The relationship among their activities and phenolic profiles was also studied. Three WL, from Cabernet, Mazuela, and Garnacha grape varieties, were firstly selected based on their ACEi properties. Their phenolic profiles were fully characterized by UHPLC-ESI-Q-TOF-MS. Then, their potential antihypertensive effects were evaluated in spontaneously hypertensive rats (SHR). BP was recorded before and after their oral administrations (2, 4, 6, 8, 24, and 48 h) at a dose of 5 mL/kg bw. Cabernet WL (CWL) exhibited a potent antihypertensive activity, similar to that obtained with the drug Captopril. This BP-lowering effect was related to the high amount of anthocyanins and flavanols present in these lees. In addition, a potential hypotensive effect of CWL was discarded in normotensive Wistar-Kyoto rats. Finally, the ACEi and antihypertensive activities of CWL coming from a different harvest were confirmed. Our results suggest the potential of CWL for controlling arterial BP, opening the door to commercial use within the wine industry.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/farmacologia , Anti-Hipertensivos/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Polifenóis/farmacologia , Vitis/química , Vinho , Animais , Captopril/farmacologia , Hipertensão/tratamento farmacológico , Masculino , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY
13.
Oxid Med Cell Longev ; 2021: 5575545, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33763167

RESUMO

Valsartan belongs to angiotensin II type 1 (AT1) receptor blockers (ARB) used in cardiovascular diseases like heart failure and hypertension. Except for its AT1-antagonism, another mechanism of drug action has been suggested in recent research. One of the supposed actions refers to the positive impact on redox balance and reducing protein glycation. Our study is aimed at assessing the antiglycooxidant properties of valsartan in an in vitro model of oxidized bovine serum albumin (BSA). Glucose, fructose, ribose, glyoxal (GO), methylglyoxal (MGO), and chloramine T were used as glycation or oxidation agents. Protein oxidation products (total thiols, protein carbonyls (PC), and advanced oxidation protein products (AOPP)), glycooxidation products (tryptophan, kynurenine, N-formylkynurenine, and dityrosine), glycation products (amyloid-ß structure, fructosamine, and advanced glycation end products (AGE)), and albumin antioxidant activity (total antioxidant capacity (TAC), DPPH assay, and ferric reducing antioxidant power (FRAP)) were measured in each sample. In the presence of valsartan, concentrations of protein oxidation and glycation products were significantly lower comparing to control. Moreover, albumin antioxidant activity was significantly higher in those samples. The drug's action was comparable to renowned antiglycation agents and antioxidants, e.g., aminoguanidine, metformin, Trolox, N-acetylcysteine, or alpha-lipoic acid. The conducted experiment proves that valsartan can ameliorate protein glycation and oxidation in vitro in various conditions. Available animal and clinical studies uphold this statement, but further research is needed to confirm it, as reduction of protein oxidation and glycation may prevent cardiovascular disease development.


Assuntos
Antioxidantes/farmacologia , Valsartana/farmacologia , Acetilcisteína/farmacologia , Animais , Captopril/farmacologia , Cloraminas , Cromanos/farmacologia , Frutose , Glucose , Glicosilação , Humanos , Metformina/farmacologia , Oxirredução , Aldeído Pirúvico , Soroalbumina Bovina/metabolismo , Ácido Tióctico/farmacologia , Compostos de Tosil
14.
Endocr Pract ; 27(4): 326-333, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33779561

RESUMO

OBJECTIVE: The saline suppression test (SST) and captopril challenge test (CCT) are commonly used confirmatory tests for primary aldosteronism (PA). Seated SST (SSST) has been reported to be superior to recumbent SST. Whether SSST is better than CCT remains unclear. We aimed to compare the diagnostic accuracy of SSST and CCT in a prospective study. METHODS: Hypertensive patients at a high risk of PA were consecutively included. Patients with an aldosterone-renin ratio of ≥1.0 ng/dL/µIU/mL were asked to complete SSST, CCT, and the fludrocortisone suppression test (FST). Using FST as a reference standard (plasma aldosterone concentration [PAC] post FST ≥ 6.0 ng/dL), area under the receiver-operating characteristic curve (AUC), sensitivity, and specificity of SSST and CCT were calculated, and multiple regression analyses were performed to identify potential factors leading to false diagnosis. RESULTS: A total of 196 patients diagnosed with PA and 73 with essential hypertension completed the study. Using PAC post SSST and PAC post CCT to confirm PA, SSST and CCT had comparable AUCs (AUCSSST 0.87 [95% CI 0.82-0.91] vs AUCCCT 0.88 [0.83-0.95], P = .646). When PAC post SSST and post CCT were set at 8.5 and 11 ng/dL, respectively, the sensitivity and specificity of SSST (0.72 [0.65, 0.78] and 0.86 [0.76, 0.93]) and CCT (0.73 [0.67, 0.80] and 0.85 [0.75, 0.92]) were not significantly different. In the multiple regression analyses, 1-SD increment of sodium intake resulted in a 40% lower risk of false diagnosis with SSST. CONCLUSION: SSST and CCT have comparable diagnostic accuracy. Insufficient sodium intake decreases the diagnostic efficiency of SSST but not of CCT. Since CCT is simpler and cheaper, it is preferred over SSST.


Assuntos
Hiperaldosteronismo , Hipertensão , Aldosterona , Captopril , Humanos , Hiperaldosteronismo/diagnóstico , Hipertensão/diagnóstico , Estudos Prospectivos , Renina
15.
Cardiol Young ; 31(8): 1315-1322, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33536102

RESUMO

OBJECTIVES: To assess the efficacy and safety of captopril, simvastatin, and L-carnitine as cardioprotective drugs in children with type 1 diabetes mellitus on different echocardiographic parameters, electrocardiographic parameter, lipid profile, and carotid intima-media thickness. METHODS: This randomised controlled trial was conducted on 100 children with type 1 diabetes mellitus for more than 3 years during the period from September 2018 to June 2020. Fifty healthy children of matched age and sex served as a control group. The patients were randomly assigned into four groups (25 children each): no-treatment group who received no cardioprotective drug, simvastatin group who received simvastatin (10-20 mg/day), captopril group who received captopril (0.2 mg/kg/day), and L-carnitine group who received L-carnitine (50 mg/kg/day) for 4 months. Lipid profile, serum troponin I, carotid intima-media thickness, and echocardiographic examinations were performed on all included children before and after the treatment. RESULTS: Total cholesterol and low-density lipoprotein were significantly decreased in children who received simvastatin or L-carnitine. Triglycerides significantly decreased only in children who received simvastatin. High-density lipoprotein significantly increased in simvastatin and L-carnitine groups only. Serum troponin I decreased significantly in all the three treatment groups. Carotid intima-media thickness showed no significant change in all treatment groups. Echocardiographic parameters significantly improved in simvastatin, L-carnitine, and captopril groups. CONCLUSION: Captopril, simvastatin, and L-carnitine have a significant beneficial effect on cardiac functions in children with type 1 diabetes mellitus. However, only simvastatin and L-carnitine have a beneficial effect on the lipid profile. The drugs were safe and well tolerated.Clinical trial registration: The clinical trial was registered at www.clinicaltrial.gov (NCT03660293).


Assuntos
Diabetes Mellitus Tipo 1 , Preparações Farmacêuticas , Captopril , Carnitina , Espessura Intima-Media Carotídea , Criança , Diabetes Mellitus Tipo 1/tratamento farmacológico , Humanos , Sinvastatina/uso terapêutico
16.
Clin Sci (Lond) ; 135(6): 793-810, 2021 03 26.
Artigo em Inglês | MEDLINE | ID: mdl-33625485

RESUMO

Until now, renin-angiotensin system (RAS) hyperactivity was largely thought to result from angiotensin II (Ang II)-dependent stimulation of the Ang II type 1 receptor (AT1R). Here we assessed the role of soluble (pro)renin receptor (sPRR), a product of site-1 protease-mediated cleavage of (pro)renin receptor (PRR), as a possible ligand of the AT1R in mediating: (i) endothelial cell dysfunction in vitro and (ii) arterial dysfunction in mice with diet-induced obesity. Primary human umbilical vein endothelial cells (HUVECs) treated with a recombinant histidine-tagged sPRR (sPRR-His) exhibited IκBα degradation concurrent with NF-κB p65 activation. These responses were secondary to sPRR-His evoked elevations in Nox4-derived H2O2 production that resulted in inflammation, apoptosis and reduced NO production. Each of these sPRR-His-evoked responses was attenuated by AT1R inhibition using Losartan (Los) but not ACE inhibition using captopril (Cap). Further mechanistic exploration revealed that sPRR-His activated AT1R downstream Gq signaling pathway. Immunoprecipitation coupled with autoradiography experiments and radioactive ligand competitive binding assays indicate sPRR directly interacts with AT1R via Lysine199 and Asparagine295. Important translational relevance was provided by findings from obese C57/BL6 mice that sPRR-His evoked endothelial dysfunction was sensitive to Los. Besides, sPRR-His elevated blood pressure in obese C57/BL6 mice, an effect that was reversed by concurrent treatment with Los but not Cap. Collectively, we provide solid evidence that the AT1R mediates the functions of sPRR during obesity-related hypertension. Inhibiting sPRR signaling should be considered further as a potential therapeutic intervention in the treatment and prevention of cardiovascular disorders involving elevated blood pressure.


Assuntos
Hipertensão/fisiopatologia , Receptor Tipo 1 de Angiotensina/efeitos dos fármacos , Receptores de Superfície Celular/metabolismo , Animais , Anti-Hipertensivos/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Captopril/farmacologia , Dieta Hiperlipídica/efeitos adversos , Células Endoteliais da Veia Umbilical Humana , Humanos , Peróxido de Hidrogênio , Losartan/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade , Sistema Renina-Angiotensina/efeitos dos fármacos
17.
Molecules ; 26(4)2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33562585

RESUMO

In the present research, a zone fluidics-based automated sensor for the analysis of captopril in in vitro dissolution samples is reported. Captopril is reacted under flow conditions with Ni(II) (10 mmol L-1) in alkaline medium (0.15% v/v NH3) to form a stable derivate, which is monitored spectrophotometrically at 340 nm. The chemical and instrumental parameters were carefully investigated and optimized. The validation of the developed method was performed in the range of 5 to 120% of the expected maximum concentration using the accuracy profiles as a graphical decision-making tool. The ß-expectation tolerance intervals did not exceed the acceptance criteria of ±10%, which means that 95% of future results will be encompassed in the defined bias limits. The variation of the relative bias ranged between -2.3% and 3.5% and the RSD values for repeatability and intermediate precision were lower than 2.3% in all cases. The limit of detection (LOD), and the lower and the upper limit of quantification (LLOQ, ULOQ) were satisfactory and found to be 1%, 5% and 120% (corresponding to 0.6, 2.78 and 66.67 µg mL-1 in dissolution medium). The developed method was successfully applied for the analysis of captopril in dissolution tests of two commercially available batches.


Assuntos
Captopril/química , Técnicas de Química Analítica/instrumentação , Automação , Solubilidade
18.
Sci Rep ; 11(1): 2215, 2021 01 26.
Artigo em Inglês | MEDLINE | ID: mdl-33500491

RESUMO

Brain radiation can occur from treatment of brain tumors or accidental exposures. Brain radiation has been rarely considered, though, as a possible tool to alter protein levels involved in neurodegenerative disorders. We analyzed possible molecular and neuropathology changes of phosphorylated-Tau (pTau), all-Tau forms, ß-tubulin, amyloid precursor protein (APP), glial fibrillary acidic protein (GFAP), ionized calcium binding adaptor molecule 1 (IBA-1), myelin basic protein (MBP), and GAP43 in Frontal Cortex (FC), Hippocampus (H) and Cerebellum (CRB) of swine brains following total-body low-dose radiation (1.79 Gy). Our data show that radiated-animals had lower levels of pTau in FC and H, APP in H and CRB, GAP43 in CRB, and higher level of GFAP in H versus sham-animals. These molecular changes were not accompanied by obvious neurohistological changes, except for astrogliosis in the H. These findings are novel, and might open new perspectives on brain radiation as a potential tool to interfere with the accumulation of specific proteins linked to the pathogenesis of various neurodegenerative disorders.


Assuntos
Peptídeos beta-Amiloides/metabolismo , Encéfalo/metabolismo , Encéfalo/efeitos da radiação , Mamíferos/metabolismo , Proteínas tau/metabolismo , Animais , Captopril/farmacologia , DNA Polimerase beta/metabolismo , Relação Dose-Resposta à Radiação , Proteína GAP-43/metabolismo , Proteína Glial Fibrilar Ácida/metabolismo , Fosforilação/efeitos da radiação , Suínos , Tubulina (Proteína)/metabolismo , Irradiação Corporal Total
19.
Int J Med Sci ; 18(4): 975-983, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33456355

RESUMO

Pathological cutaneous scars, with aberrant extracellular matrix accumulation, have multiple origins. Antihypertensive medications, such as calcium channel blockers, have been used to treat pathological scars. However, a relationship between angiotensin-converting enzyme (ACE) inhibitors, pathological scars, and blood pressure (BP) has never been reported. Here, we aimed to compare the differences in scar development and the effects of the administration of systemic ACE inhibitor on scar tissue in a normotensive rat, the Wistar Kyoto rat (WKY), a hypertensive rat, and the spontaneously hypertensive rat (SHR). Using an 8-mm punch, we created two full-thickness skin defects in a total of 32 rats (16 WKY and 16 SHR) to obtain a total of 64 wounds. We established control WKY (n = 16), captopril-treated WKY (n = 16), control SHR (n = 16), and captopril-treated SHR (n = 16) groups and started captopril (100 mg/g per day) treatment on day 21 in the appropriate groups. The BP of all groups was measured at 0, 3, and 5 weeks. The scar area was measured by histopathological examination, and scarring was expressed in terms of scar area and fibroblast and capillary counts. The expression of heat shock protein (HSP) 47, type I and III collagens, alpha-smooth muscle actin (α-SMA), Ki67, and vascular endothelial growth factor (VEGF) was investigated using immunohistochemistry. The scar area and fibroblast count were significantly higher in control SHR than in control WKY. The scar area, fibroblast count, and capillary count were significantly smaller in captopril-treated SHR than in control SHR. Immunostaining for α-SMA, Ki67, and VEGF also showed a noticeable decrease in scarring in the treated SHR compared with that in control SHR. Thus, BP affects scar development in a rat model, and an ACE inhibitor is more effective at reducing scars in hypertensive rats than in normotensive rats.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Captopril/administração & dosagem , Cicatriz/tratamento farmacológico , Hipertensão/tratamento farmacológico , Administração Oral , Animais , Pressão Sanguínea/efeitos dos fármacos , Cicatriz/etiologia , Cicatriz/patologia , Modelos Animais de Doenças , Humanos , Hipertensão/complicações , Masculino , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Pele/efeitos dos fármacos , Pele/patologia
20.
Eur J Pharmacol ; 895: 173870, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33476653

RESUMO

Fibromyalgia is a potentially disabling chronic disease, characterized by widespread pain and a range of comorbidities such as hypertension. Among the mechanisms involved in fibromyalgia-like pain symptoms are kinins and their B1 and B2 receptors. Moreover, angiotensin I converting enzyme (ACE) inhibitors, commonly used as antihypertensive drugs, can enhance pain by blocking the degradation of peptides such as substance P and bradykinin, besides enhancing kinin receptors signalling. We investigated the effect of ACE inhibitors on reserpine-induced fibromyalgia-like pain symptoms and the involvement of kinins in this effect in mice. Nociceptive parameters (mechanical and cold allodynia and overt nociception) were evaluated after ACE inhibitors administration in mice previously treated with reserpine. The role of kinin B1 and B2 receptors was investigated using pharmacological antagonism. Additionally, bradykinin levels, as well as the activity of ACE and kininase I, were measured in the sciatic nerve, spinal cord and cerebral cortex of the mice. The ACE inhibitors enalapril and captopril enhanced reserpine-induced mechanical allodynia, and this increase was prevented by kinin B1 and B2 receptor antagonists. Substance P and bradykinin caused overt nociception and increased mechanical allodynia in animals treated with reserpine. Reserpine plus ACE inhibitors increased bradykinin-related peptide levels and inhibited ACE activity in pain modulation structures. Since hypertension is a frequent comorbidity affecting fibromyalgia patients, hypertension treatment with ACE inhibitors in these patients should be reviewed once this could enhance fibromyalgia-like pain symptoms. Thus, the treatment of hypertensive patients with fibromyalgia could include other classes of antihypertensive drugs, different from ACE inhibitors.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/toxicidade , Fibromialgia/induzido quimicamente , Sistema Nervoso/efeitos dos fármacos , Dor Nociceptiva/induzido quimicamente , Limiar da Dor/efeitos dos fármacos , Peptidil Dipeptidase A/metabolismo , Receptores da Bradicinina/metabolismo , Animais , Comportamento Animal/efeitos dos fármacos , Captopril/toxicidade , Modelos Animais de Doenças , Enalapril/toxicidade , Fibromialgia/enzimologia , Fibromialgia/fisiopatologia , Masculino , Camundongos , Sistema Nervoso/enzimologia , Sistema Nervoso/fisiopatologia , Dor Nociceptiva/enzimologia , Dor Nociceptiva/fisiopatologia , Reserpina , Transdução de Sinais
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