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1.
Presse Med ; 48(12): 1445-1455, 2019 Dec.
Artigo em Francês | MEDLINE | ID: mdl-31761607

RESUMO

The Hormonal assessment of Arterial Hypertension (HTA) is an important part of the balance of resistant hypertension. This assessment - going well beyond the search for primary hyperaldosteronism (PHA) - requires a rigorous methodology and a robust experience of the nursing team within a dedicated unit: the HTA Day Hospital. If all the conditions are met and the assessment carried out well, it will allow a significant profitability since in this resistant hypertensive population it will detect a particular mechanism or secondary hypertension in 70% of patients. Since the diagnosis of PHA is essentially biological, the proper execution of the various stages of the assessment is essential to its documentation.


Assuntos
Técnicas de Diagnóstico Endócrino , Hormônios/análise , Hipertensão/diagnóstico , Aldosterona/análise , Aldosterona/sangue , Anti-Hipertensivos/uso terapêutico , Análise Química do Sangue/métodos , Análise Química do Sangue/normas , Diagnóstico Diferencial , Técnicas de Diagnóstico Endócrino/normas , Resistência a Medicamentos/efeitos dos fármacos , Hormônios/sangue , Humanos , Hiperaldosteronismo/diagnóstico , Hipertensão/sangue , Hipertensão/tratamento farmacológico , Hipertensão/etiologia , Renina/análise , Renina/sangue
3.
Mil Med ; 184(5-6): e298-e302, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30371879

RESUMO

INTRODUCTION: Low distal aortic flow via partial aortic occlusion (AO) may mitigate ischemia induced by resuscitative endovascular balloon occlusion of the aorta (REBOA). We compared endocrine effects of a novel simulated partial AO strategy, endovascular variable aortic control (EVAC), with simulated REBOA in a swine model. MATERIALS AND METHODS: Aortic flow in 20 swine was routed from the supraceliac aorta through an automated extracorporeal circuit. Following liver injury-induced hemorrhagic shock, animals were randomized to control (unregulated distal flow), simulated REBOA (no flow, complete AO), or simulated EVAC (distal flow of 100-300 mL/min after 20 minutes of complete AO). After 90 minutes, damage control surgery, resuscitation, and full flow restoration ensued. Critical care was continued for 4.5 hours or until death. RESULTS: Serum angiotensin II concentration was higher in the simulated EVAC (4,769 ± 624 pg/mL) than the simulated REBOA group (2649 ± 429) (p = 0.01) at 180 minutes. There was no detectable difference in serum renin [simulated REBOA: 231.3 (227.9-261.4) pg/mL; simulated EVAC: 294.1 (231.2-390.7) pg/mL; p = 0.27], aldosterone [simulated EVAC: 629 (454-1098), simulated REBOA: 777 (575-1079) pg/mL, p = 0.53], or cortisol (simulated EVAC: 141 ± 12, simulated REBOA: 127 ± 9 ng/mL, p = 0.34) concentrations between groups. CONCLUSIONS: Simulated EVAC was associated with higher serum angiotensin II, which may have contributed to previously reported cardiovascular benefits. Future studies should evaluate the renal effects of EVAC and the concomitant therapeutic use of angiotensin II.


Assuntos
Aorta/cirurgia , Oclusão com Balão/efeitos adversos , Sistema Endócrino/enzimologia , Aldosterona/análise , Aldosterona/sangue , Angiotensina II/análise , Angiotensina II/sangue , Animais , Aorta/enzimologia , Oclusão com Balão/métodos , Modelos Animais de Doenças , Sistema Endócrino/irrigação sanguínea , Hidrocortisona/análise , Hidrocortisona/sangue , Renina/análise , Renina/sangue , Estatísticas não Paramétricas , Suínos
4.
Arq Bras Oftalmol ; 81(6): 494-499, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30231160

RESUMO

PURPOSE: Pseudoexfoliation syndrome has been linked to impaired function of the heart and blood vessels. We conducted a study to investigate the role of the renin-angiotensin system in the etiopathogenesis of pseudoexfoliation syndrome. METHODS: The subjects were 14 patients with pseudoexfoliation syndrome and 14 healthy controls who underwent cataract extraction. Preoperative 5-ml samples of peripheral venous blood and perioperative aqueous humor were collected from the patients in both groups. Plasma and aqueous humor renin levels were analyzed by an immunoradiometric method, and angiotensin II levels were analyzed by radioimmunassay. SPSS version 16.0 was used for statistical analyses. A p-value <0.05 was considered to indicate a statistically significant difference. RESULTS: The mean ages of the patients in pseudoexfoliation and control groups were 71.7 ± 7.1 and 67.4 ± 9.3 years, respectively (p=0.140). The median aqueous humor renin level was 7.73 pg/ml (4.15-21) in the control group and 11.95 pg/ml (3.75-18.54) in pseudoexfoliation group (p=0.022). There were no differences between the two groups in the plasma renin, plasma angiotensin II, or aqueous humor angiotensin II levels. The correlations between plasma and aqueous humor renin levels and between plasma and aqueous humor angiotensin II levels were examined separately for each group; no significant correlations were observed in pseudoexfoliation group (r=-0.440, p=0.115; r=-0.414, p=0.142) or the control group (r=-0.232, p=0.425; r=0.482, p=0.081). CONCLUSION: Aqueous humor renin levels are higher in pseudoexfoliation syndrome. The results indicate a probable role of renin-angiotensin system in pseudoexfoliation syndrome. Further studies with larger numbers of cases are needed to clarify the precise association of renin-angiotensin system with the etiopathogenesis of pseudoexfoliation syndrome.


Assuntos
Angiotensina II/análise , Síndrome de Exfoliação/etiologia , Sistema Renina-Angiotensina , Renina/análise , Idoso , Idoso de 80 Anos ou mais , Humor Aquoso/metabolismo , Catarata/sangue , Extração de Catarata , Síndrome de Exfoliação/sangue , Síndrome de Exfoliação/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Período Pré-Operatório , Estudos Prospectivos
5.
Mol Med Rep ; 16(5): 7432-7438, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28944831

RESUMO

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are the clinical manifestations of severe lung damage and respiratory failure. ALI and ARDS result are associated with high mortality in patients. At present, no effective treatments for ALI and ARDS exist. It is established that vitamin D exhibits anti­inflammatory effects, however, the specific effect of vitamin D on ALI remains largely unknown. The aim of the present study was to investigate whether, and by which mechanism, vitamin D alleviates lipopolysaccharide (LPS)­induced ALI. The results demonstrated that a vitamin D agonist, calcitriol, exhibited a beneficial effect on LPS­induced ALI in rats; calcitriol pretreatment significantly improved LPS­induced lung permeability, as determined using Evans blue dye. Results from reverse transcription­quantitative polymerase chain reaction, western blotting and ELISA analysis demonstrated that calcitriol also modulated the expression of members of the renin­angiotensin system (RAS), including angiotensin (Ang) I­converting enzymes (ACE and ACE2), renin and Ang II, which indicates that calcitriol may exert protective effects on LPS­induced lung injury, at least partially, by regulating the balance between the expression of members of the RAS. The results of the present study may provide novel targets for the future treatment of ALI.


Assuntos
Angiotensina II/análise , Lipopolissacarídeos/toxicidade , Sistema Renina-Angiotensina/efeitos dos fármacos , Renina/análise , Vitamina D/farmacologia , Lesão Pulmonar Aguda/etiologia , Lesão Pulmonar Aguda/metabolismo , Animais , Líquido da Lavagem Broncoalveolar/química , Células Cultivadas , Células Endoteliais/citologia , Células Endoteliais/metabolismo , Ensaio de Imunoadsorção Enzimática , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Masculino , Microvasos/citologia , Peptidil Dipeptidase A/genética , Peptidil Dipeptidase A/metabolismo , Ratos , Ratos Wistar , Receptor Tipo 1 de Angiotensina/genética , Receptor Tipo 1 de Angiotensina/metabolismo , Receptor Tipo 2 de Angiotensina/genética , Receptor Tipo 2 de Angiotensina/metabolismo
6.
Rev. lab. clín ; 10(3): 148-153, jul.-sept. 2017. tab, ilus
Artigo em Espanhol | IBECS | ID: ibc-164882

RESUMO

El aldosteronismo primario se considera una de las causas más comunes de hipertensión secundaria. Los datos indican que puede ocurrir en hasta el 5-15% de los pacientes con hipertensión. Aunque esta enfermedad sigue siendo un reto diagnóstico considerable, el reconocimiento de la condición es crítica, debido a que la hipertensión asociada al aldosteronismo primario a menudo se puede curar con la intervención quirúrgica o médica adecuada. El diagnóstico se realiza en 3 etapas, que implican un cribado inicial, una confirmación del diagnóstico, y una clasificación del subtipo específico de aldosteronismo primario. Se describe el caso de un paciente con hipertensión resistente e hipopotasemia. La prueba inicial incluye la cuantificación de las concentraciones de aldosterona y actividad de renina en plasma. En nuestro laboratorio la medida de estos 2 parámetros se realizó por radioinmunoanálisis. En este caso, el paciente tenía elevado el cociente aldosterona/renina y la producción de aldosterona de forma autónoma se confirmó con una prueba de supresión con sobrecarga intravenosa de sodio. Una vez confirmado el aldosteronismo primario, se determinó el subtipo para guiar el tratamiento. La prueba inicial en la evaluación del subtipo es la tomografía axial computarizada (TAC) de las glándulas suprarrenales. Además, si se considera el tratamiento quirúrgico, el muestreo de la vena adrenal es el método más preciso para distinguir entre la producción de aldosterona adrenal unilateral o bilateral. En este caso se muestra como el laboratorio juega un papel fundamental en el diagnóstico del aldosteronismo primario, con el fin de lograr el tratamiento óptimo (AU)


Primary aldosteronism is considered one of the most common causes of secondary hypertension. Data indicate that it may occur in as many as 5-15% of patients with hypertension. Although it is still a considerable diagnostic challenge, recognising the condition is critical as primary aldosteronism associated hypertension can often be cured with the proper surgical or medical intervention. The diagnosis is generally 3-tiered, involving an initial screening, a confirmation of the diagnosis, and a determination of the specific subtype of primary aldosteronism. The case is described of a patient with resistant hypertension and hypokalaemia. The initial tests included the measurement of plasma aldosterone levels and plasma rennin activity, which is by Radioimmunoassay in our laboratory. In this case, the patient had an increased aldosterone/renin ratio, and the free aldosterone production was confirmed with an aldosterone suppression test (intravenous salt loading test). Once primary aldosteronism was confirmed, the subtype was determined to guide treatment. The initial test in subtype evaluation is computed axial tomography imaging (CAT) of the adrenal glands. Furthermore, if surgical treatment is considered, adrenal vein sampling is the most accurate method for distinguishing between unilateral and bilateral adrenal aldosterone production. In this case is shown as the laboratory plays a fundamental role in the diagnosis of primary aldosteronism, in order to achieve the optimal treatment (AU)


Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Hiperaldosteronismo/diagnóstico , Hiperaldosteronismo/patologia , Aldosterona/análise , Cateterismo/instrumentação , Hipertensão/diagnóstico , Valores de Referência , Renina/análise , Diagnóstico Diferencial , Hipopotassemia/diagnóstico , Hipopotassemia/patologia , Programas de Rastreamento/métodos , Algoritmos , Doenças do Córtex Suprarrenal/diagnóstico , Doenças do Córtex Suprarrenal/cirurgia
7.
Hypertension ; 70(2): 334-341, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28652474

RESUMO

Measurement of plasma aldosterone and renin concentration, or activity, is useful for selecting antihypertensive agents and detecting hyperaldosteronism in hypertensive patients. However, it takes several days to get results when measured by radioimmunoassay and development of more rapid assays has been long expected. We have developed chemiluminescent enzyme immunoassays enabling the simultaneous measurement of both aldosterone and renin concentrations in 10 minutes by a fully automated assay using antibody-immobilized magnetic particles with quick aggregation and dispersion. We performed clinical validation of diagnostic ability of this newly developed assay-based screening of 125 patients with primary aldosteronism from 97 patients with essential hypertension. Results of this novel assay significantly correlated with the results of radioimmunoassay (aldosterone, active renin concentration, and renin activity) and liquid chromatography-tandem mass spectrometry (aldosterone). The analytic sensitivity of this particularly novel active renin assay was 0.1 pg/mL, which was better than that of radioimmunoassay (2.0 pg/mL). The ratio of aldosterone-to-renin concentrations of 6.0 (ng/dL per pg/mL) provided 92.0% sensitivity and 76.3% specificity as a cutoff for differentiating primary aldosteronism from essential hypertension. This novel measurement is expected to be a clinically reliable alternative for conventional radioimmunoassay and to provide better throughput and cost effectiveness in diagnosis of hyperaldosteronism from larger numbers of hypertensive patients in clinical settings.


Assuntos
Aldosterona , Anti-Hipertensivos/uso terapêutico , Hiperaldosteronismo , Hipertensão , Medições Luminescentes/métodos , Renina , Adulto , Aldosterona/análise , Aldosterona/sangue , Cromatografia Líquida/métodos , Pesquisa Comparativa da Efetividade , Feminino , Humanos , Hiperaldosteronismo/sangue , Hiperaldosteronismo/diagnóstico , Hipertensão/tratamento farmacológico , Hipertensão/etiologia , Imunoensaio/métodos , Japão , Masculino , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Seleção de Pacientes , Testes Imediatos , Radioimunoensaio/métodos , Renina/análise , Renina/sangue , Reprodutibilidade dos Testes
8.
Ann Med ; 49(6): 525-533, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28358246

RESUMO

BACKGROUND: Direct renin inhibition (DRI) is clinically inferior to other blockers of the renin-angiotensin system (RAS). Thus far, the underlying molecular causes of this finding remain unknown. METHODS: Twenty four patients with non-diabetic chronic kidney disease (CKD) stages III-IV and albuminuria were randomized to DRI or angiotensin receptor blocker (ARB). Employing a novel mass-spectrometry method, the concentrations of renin, aldosterone and plasma angiotensin peptides [Ang I, Ang II, Ang-(1-7), Ang-(1-5), Ang-(2-8), Ang-(3-8)] were quantified before and after an 8-week treatment. RESULTS: While blood pressure, renal function and albuminuria decreased comparably in both groups, profound RAS component differences were observed: DRI led to a massive renin increase, while suppressing both vasoconstrictive (Ang I and Ang II) and vasodilatory RAS metabolites (Ang-(1-7) and Ang-(1-5)). In contrast, ARB led to a four-fold increase of Ang I and Ang II, while Ang-(1-7) and Ang-(1-5) increased moderately but significantly. With ARB treatment, a decreased aldosterone-to-Ang II ratio suggested efficacy in blocking AT1 receptor. CONCLUSIONS: DRI therapy abolishes all RAS effector peptides. ARB increases both vasoconstrictive and vasodilative angiotensins, while this is accompanied by efficient blockade of vasoconstrictive effects. These differential molecular regulations should be considered when selecting optimal antihypertensive and disease-modifying therapy in CKD patients. Key messages Direct renin inhibition leads to a complete and lasting abolition of both classical and alternative RAS components. Angiotensin receptor blockade leads to effective receptor blockade and up-regulation of alternative RAS components. Differential molecular regulations of the RAS should be considered when selecting optimal antihypertensive and disease-modifying therapy in CKD patients.


Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Oligopeptídeos/farmacologia , Fragmentos de Peptídeos/sangue , Inibidores de Proteases/farmacologia , Insuficiência Renal Crônica/tratamento farmacológico , Adulto , Idoso , Albuminúria/etiologia , Albuminúria/metabolismo , Aldosterona/análise , Angiotensinas/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/metabolismo , Renina/análise , Sistema Renina-Angiotensina/efeitos dos fármacos
9.
Biosens Bioelectron ; 84: 120-5, 2016 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-26746799

RESUMO

Antibody-based immunosensors are relatively less accessible to a wide variety of unreachable targets, such as low-molecular-weight biomarkers that represent a rich untapped source of disease-specific diagnostic information. Here, we present a peptide aptamer-based electrochemical sensor technology called 'PEP-on-DEP' to detect less accessible target molecules, such as renin, and to improve the quality of life. Peptide-based aptamers represent a relatively smart class of affinity binders and show great promise in biosensor development. Renin is involved in the regulation of arterial blood pressure and is an emerging biomarker protein for predicting cardiovascular risk and prognosis. To our knowledge, no studies have described aptamer molecules that can be used as new potent probes for renin. Here, we describe a portable electrochemical biosensor platform based on the newly identified peptide aptamer molecules for renin. We constructed a randomized octapeptide library pool with diversified sequences and selected renin specific peptide aptamers using cDNA display technology. We identified a few peptide aptamer sequences with a KD in the µM binding affinity range for renin. Next, we grafted the selected peptide aptamers onto gold nanoparticles and detected renin in a one-step competitive assay using our originally developed DEP (Disposable Electrochemical Printed) chip and a USB powered portable potentiostat system. We successfully detected renin in as little as 300ngmL(-1) using the PEP-on-DEP method. Thus, the generation and characterization of novel probes for unreachable target molecules by merging a newly identified peptide aptamer with electrochemical transduction allowed for the development of a more practical biosensor that, in principle, can be adapted to develop a portable, low-cost and mass-producible biosensor for point-of-care applications.


Assuntos
Aptâmeros de Peptídeos/química , Técnicas Biossensoriais/instrumentação , Técnicas Eletroquímicas/instrumentação , Sistemas Automatizados de Assistência Junto ao Leito , Renina/análise , Biomarcadores/análise , Desenho de Equipamento , Ouro/química , Humanos , Nanopartículas Metálicas/química
10.
Iran J Kidney Dis ; 9(6): 440-8, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26552350

RESUMO

INTRODUCTION: Renin synthesis and release is the rate-limiting step in the renin-angiotensin system, because cyclic adenosine monophosphate (cAMP) has been identified as dominant pathway for renin gene expression, and cAMP response element-binding protein (CREB) is found in the human and mouse renin promoter. This study aimed to evaluate the role of CREB in expression of the renin gene. MATERIALS AND METHODS: We created conditional deletion of CREB in mice with low-sodium diet, specifically in renin cells of the kidney. To assess the effect of CREB on renin expression, immunostaining of renin was used in samples from wild-type mice and mice with gene knock-down of CREB. Cyclic AMP response element-binding-protein-binding protein (CBP) and p300 were measured in cultured renin cells of the mice, and RNA detection was done with real-time polymerase chain reaction. RESULTS: With low-sodium diet, renin was expressed along the whole wall of the afferent glomerular arterioles in wild-type mice, while there was no increase or even decrease in renin expression in CREB-specific deletion mice; RNA level of renin in cultured cells decreased by 50% with single knock-down of CREB, CBP, or p300, and decreased 70% with triple knock-down of CREB, CBP, and p300. CONCLUSIONS: This study found that CREB was important for renin synthesis and the role of CREB can be achieved through the recruitment of co-activators CBP and p300.


Assuntos
Arteríolas/química , Proteína de Ligação a CREB/genética , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , Proteína p300 Associada a E1A/genética , Sistema Justaglomerular/química , RNA Mensageiro/análise , Renina/genética , Animais , Proteína de Ligação a CREB/análise , Células Cultivadas , Colforsina/farmacologia , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/análise , Regulação para Baixo/genética , Proteína p300 Associada a E1A/análise , Expressão Gênica , Técnicas de Silenciamento de Genes , Imuno-Histoquímica , Sistema Justaglomerular/irrigação sanguínea , Sistema Justaglomerular/citologia , Camundongos , Músculo Liso Vascular/citologia , Miócitos de Músculo Liso/química , RNA Interferente Pequeno/genética , Renina/análise , Sódio na Dieta/administração & dosagem , Transfecção
11.
Rev Prat ; 65(6): 817-21, 2015 Jun.
Artigo em Francês | MEDLINE | ID: mdl-26298907

RESUMO

Primary aldosteronism affects 6% of hypertensive patients. The diagnosis should be suspected in any patient with severe or resistant hypertension or hypertension associated with hypokalemia. The screening test consists on the assessment of the aldosterone to renin ratio. In case of an elevated ratio, the diagnosis of primary aldosteronism is confirmed by either elevated concentrations of basal plasma and/or urinary aldosterone or absence of suppression of aldosterone during dynamic test (including the saline infusion test). CT aims to ensure the absence of adrenal carcinoma and to study the morphology of the adrenals. The unilateral or bilateral type of aldosterone secretion is based on the realization of an adrenal venous sampling. When the hypersecretion is unilateral, the treatment consists of adrenalectomy leading to cure of hypertension in 42% of cases, improvement in 40% of cases. For patient with bilateral disease or who don't want to undergo surgery, treatment is based on spironolactone usually at doses of 25 or 50 mg in combination with other antihypertensives drugs such as diuretics or calcium channel blockers.


Assuntos
Hiperaldosteronismo/diagnóstico , Hiperaldosteronismo/terapia , Neoplasias do Córtex Suprarrenal/diagnóstico , Neoplasias do Córtex Suprarrenal/cirurgia , Adrenalectomia , Adenoma Adrenocortical/diagnóstico , Adenoma Adrenocortical/cirurgia , Aldosterona/análise , Algoritmos , Anti-Hipertensivos/uso terapêutico , Bloqueadores dos Canais de Cálcio/uso terapêutico , Humanos , Hiperaldosteronismo/etiologia , Hipertensão/etiologia , Hipertensão/terapia , Hipopotassemia/diagnóstico , Renina/análise
12.
Ir J Med Sci ; 184(2): 297-304, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24664631

RESUMO

BACKGROUND: Urinary angiotensinogen (AGT) mainly derives from the AGT produced in proximal tubular cells. Evidence exists that supports the correlation between urinary AGT and circulating AGT. AIM: To investigate the role of urinary AGT as a potential biomarker of intrarenal renin-angiotensin system activity in Chinese chronic kidney disease (CKD) patients. METHODS: ELISA-based method used to quantify urinary AGT. Analyzed the relationship between urinary AGT and intrarenal angiotensin II (Ang II) activity in 128 CKD patients. ELISA was applied to measure the urinary and plasma renin activity, AGT, Ang II and aldosterone. Furthermore expression levels of intrarenal renin, AGT, Ang II and Ang II receptor were examined by immunohistochemistry staining (IHCS) in 72 CKD patients undergoing renal biopsy. RESULTS: The logarithmic transformation Log(urinary AGT/UCre) levels showed a normal distribution. Therefore, Log(urinary AGT/UCre) levels were used for the analyses. Average urinary AGT was 2.02 ± 0.55 ng/(mg Cr). Hypertension, urinary protein, urinary Ang II and urinary type IV collagen (Col IV) positively correlated with urinary AGT. Estimated glomerular filtration rate (eGFR), urinary sodium and serum AGT negatively correlated with urinary AGT. Multiple regression analysis indicated that low serum AGT, high urinary protein, urinary Ang II and urinary Col IV correlated significantly with high urinary AGT. CONCLUSIONS: We observed positive correlation between urinary AGT and positive IHCS area of AGT, Ang II and Ang II type 1 receptor in renal tissue. These data suggest that urinary AGT might be a potential biomarker of intrarenal Ang II activity in CKD patients.


Assuntos
Angiotensina II/análise , Angiotensinogênio/urina , Hipertensão/urina , Insuficiência Renal Crônica/urina , Sistema Renina-Angiotensina/fisiologia , Renina/análise , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Aldosterona/sangue , Aldosterona/urina , Angiotensina II/metabolismo , Angiotensinogênio/análise , Grupo com Ancestrais do Continente Asiático , Biomarcadores/urina , China , Colágeno Tipo IV/urina , Feminino , Humanos , Rim/química , Masculino , Pessoa de Meia-Idade , Receptores de Angiotensina/análise , Renina/metabolismo , Adulto Jovem
13.
Clin Chim Acta ; 443: 85-93, 2015 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-25445411

RESUMO

Renin-angiotensin-aldosterone system (RAAS), participated by kidney, liver, vascular endothelium, and adrenal cortex, and counter-regulated by cardiac endocrine function, is a complex endocrine system regulating systemic functions, such as body salt and water homeostasis and vasomotion, in order to allow the accomplishment of physiological tasks, such as orthostasis, physical and emotional stimuli, and to react towards the hemorrhagic insult, in tight conjunction with other neurohormonal axes, namely the sympathetic nervous system, the endothelin and vasopressin systems. The systemic as well as the tissue RAAS are also dedicated to promote tissue remodeling, particularly relevant after damage, when chronic activation may configure as a maladaptive response, leading to fibrosis, hypertrophy and apoptosis, and organ dysfunction. RAAS activation is a fingerprint of systemic arterial hypertension, kidney dysfunction, vascular atherosclerotic disease, and is definitely an hallmark of heart failure, which rapidly shifts from organ disease to a disorder of neurohormonal regulatory systems. Chronic RAAS activation is an indirect or direct target of most effective pharmacological treatments in heart failure, such as beta-blockers, inhibitors of angiotensin converting enzyme, angiotensin receptor blockers, direct renin inhibitors, and mineralocorticoid receptor blockers. Biomarkers of RAAS activation are available, with different feasibility and accuracy, such as plasma renin activity, renin, angiotensin II, and aldosterone, which all accompany the increasing clinical severity of heart failure disease, and are well recognized prognostic factors, even in patients with optimal therapy. Polymorphisms influencing the expression and activity of RAAS pathways have been recognized as clinically relevant biomarkers, likely influencing either the individual clinical phenotype, or the response to drugs. This solid, growing evidence strongly suggests the rationale for the use of biomarkers of the RAAS activation, as a guide to tailor individual therapy in the current practice, and their implementation as a rule-in marker for future trials on novel drugs in the heart failure setting.


Assuntos
Aldosterona/metabolismo , Angiotensinas/metabolismo , Insuficiência Cardíaca/metabolismo , Renina/metabolismo , Aldosterona/análise , Angiotensinas/análise , Biomarcadores/análise , Biomarcadores/metabolismo , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Renina/análise , Reprodutibilidade dos Testes
15.
J Cardiovasc Transl Res ; 7(6): 560-9, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25030734

RESUMO

The aim of this study was to determine if renin inhibition is able to improve the survival of transplanted stem cells in a mouse model of myocardial infarction. Myocardial infarction was induced in FVB/NJ inbred mice (n = 23). Bone marrow-derived mouse mesenchymal stromal cells (mMSCs, 3 × 10(5)) expressing the reporter gene firefly luciferase were delivered intramyocardially (n = 12) and monitored non-invasively by bioluminescence imaging. A group of these mice (n = 6) received aliskiren (15 mg/kg/day) via an osmotic pump implanted subcutaneously. The survival of mMSCs was significantly increased in those animals that received aliskiren leading to a significant improvement in systolic function after myocardial infarction. Histological analysis revealed a significant reduction in inflammation and collagen deposition in those mice that received aliskiren compared to controls. Renin inhibition of the ischemic myocardium is able to modulate the microenvironment improving the survival and efficacy of transplanted mMSCs in a mouse model of myocardial infarction.


Assuntos
Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Infarto do Miocárdio/terapia , Renina/antagonistas & inibidores , Renina/análise , Animais , Sobrevivência Celular , Modelos Animais de Doenças , Seguimentos , Imuno-Histoquímica , Camundongos , Infarto do Miocárdio/patologia , Infarto do Miocárdio/fisiopatologia , Miocárdio/patologia , Prognóstico , Função Ventricular Esquerda
16.
Pediatr Nephrol ; 29(7): 1221-30, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24477978

RESUMO

BACKGROUND: Fetuses exposed to angiotensin-converting enzyme inhibitors or angiotensin receptor antagonists during the second and/or third trimesters of gestation are at high risk of developing severe complications. They consist in fetal hypotension, and anuria/oligohydramnios leading to Potter sequence, frequently associated with hypocalvaria. Most fetuses die during the pre- or postnatal period, whereas others recover normal or subnormal renal function. However, the secondary occurrence of renal failure or hypertension has been reported in children after apparent complete recovery. METHODS: In this context, we analyzed renal lesions in 14 fetus/neonates who died soon after exposure to renin-angiotensin-system (RAS) blockers. Our objective was to determine the causes for the persistence or the secondary occurrence of renal complications reported in some of the survivors. RESULTS: As previously described, renal tubular dysgenesis is usually observed. Additional lesions, such as thickening of the muscular wall of arterioles and interlobular arteries, glomerular cysts, and interstitial fibrosis, develop early during fetal life. CONCLUSION: We suggest that renal lesions that develop before birth may persist after withdrawal of the causative drugs and normalization of blood and renal perfusion pressure. Their persistence could explain the severe long-term outcome of some of these patients. Long-term study of children exposed to RAS blockers during fetal life is strongly recommended.


Assuntos
Antagonistas de Receptores de Angiotensina/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Doenças Fetais/induzido quimicamente , Túbulos Renais/anormalidades , Rim/efeitos dos fármacos , Anormalidades Induzidas por Medicamentos , Humanos , Imuno-Histoquímica , Recém-Nascido , Rim/química , Rim/patologia , Renina/análise
17.
J Am Soc Nephrol ; 24(5): 759-70, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23449534

RESUMO

Hydrogen sulfide (H2S) is an endogenous gasotransmitter with physiologic functions similar to nitric oxide and carbon monoxide. Exogenous treatment with H2S can induce a reversible hypometabolic state, which can protect organs from ischemia/reperfusion injury, but whether cystathionine γ-lyase (CSE), which produces endogenous H2S, has similar protective effects is unknown. Here, human renal tissue revealed abundant expression of CSE, localized to glomeruli and the tubulointerstitium. Compared with wild-type mice, CSE knockout mice had markedly reduced renal production of H2S, and CSE deficiency associated with increased damage and mortality after renal ischemia/reperfusion injury. Treatment with exogenous H2S rescued CSE knockout mice from the injury and mortality associated with renal ischemia. In addition, overexpression of CSE in vitro reduced the amount of reactive oxygen species produced during stress. Last, the level of renal CSE mRNA at the time of organ procurement positively associated with GFR 14 days after transplantation. In summary, these results suggest that CSE protects against renal ischemia/reperfusion injury, likely by modulating oxidative stress through the production of H2S.


Assuntos
Cistationina gama-Liase/fisiologia , Rim/irrigação sanguínea , Estresse Oxidativo , Traumatismo por Reperfusão/prevenção & controle , Adolescente , Adulto , Idoso , Animais , Sobrevivência Celular , Cistationina beta-Sintase/fisiologia , Cistationina gama-Liase/análise , Cistationina gama-Liase/genética , Dano ao DNA , Feminino , Células HEK293 , Humanos , Sulfeto de Hidrogênio/metabolismo , Rim/enzimologia , Transplante de Rim , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Renina/análise , Superóxidos/metabolismo
18.
Methods ; 56(2): 213-22, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22387391

RESUMO

An immuno-Matrix Assisted Laser Desorption/Ionization (iMALDI) method has been developed using anti-IgG beads to capture anti-AngI and anti-AngII antibodies, which are incubated with a ∼50µL plasma sample to which known amounts of stable-isotope-labeled AngI and AngII have been added. After a short incubation time, the beads are washed, placed directly on a MALDI target, and analyzed by mass spectrometry (MS) and tandem mass spectrometry (MS/MS). The iMALDI assay developed can detect and quantify angiotensin I (AngI) and angiotensin II (AngII) in human plasma. This assay has a Limit of Detection (LOD) of ∼10amol/µL (or ∼13pg/mL AngI and ∼11pg/mL AngII), at a S/N of 2:1, using only one-tenth of the antibody beads which were incubated with a 50-µL plasma sample. This LOD is within the relevant range of patient samples. Little or no angiotensin generation period is required, resulting in a rapid assay. Correlation coefficients for the standard curves are >0.99, with a linear range of 4-100fmol/µL (5-130ng/mL) and 100-2500amol/µL (106-2614pg/mL) for AngI and AngII, respectively. This duplexed assay can quantify AngI and AngII peptide levels simultaneously, in plasma from normotensive and hypertensive patients. The assay can detect changes in the levels of these peptides over time, which will allow quantitation of plasma renin and ACE activities.


Assuntos
Angiotensina II/sangue , Angiotensina I/sangue , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Angiotensina I/análise , Angiotensina I/química , Angiotensina II/análise , Angiotensina II/química , Animais , Anticorpos/química , Calibragem , Ativação Enzimática , Ensaios Enzimáticos , Humanos , Imunoglobulina G/química , Marcação por Isótopo , Limite de Detecção , Plasma/química , Valores de Referência , Renina/análise , Renina/sangue , Renina/química , Sensibilidade e Especificidade , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/instrumentação , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/normas , Espectrometria de Massas em Tandem
19.
Rev. esp. pediatr. (Ed. impr.) ; 67(6): 354-357, nov.-dic. 2011. tab, ilus
Artigo em Espanhol | IBECS | ID: ibc-101724

RESUMO

La hipopotasemia, definida como una concentración plasmática de potasio, inferior a 3,4 mEq/L, es una situación frecuente en clínica. De forma aguda y transitoria, se produce habitualmente como resultado de cambios en al distribución del potasio interno. La hipopotasemia crónica suele ser secundaria a un balance externo negativo por aumento de las pérdidas de potasio por heces u orina. Se presenta un algoritmo que permite orientar el diagnóstico de la hipokalemia de origen renal en población infantil en base a los valores de tensión arterial, los valores circulantes de renina y aldosterona y el estado del equilibrio ácido-base (AU)


Hypokalemia, defined as plasma concentration of potassium below 3.5 mEq/L, is a commonly found clinical condition. Acute and transient hypokalemia usually results from changes in the internal potassium distribution. Chronic hypokalemia is secondary to a negative external balance caused by increased losses of potassium by feces or urine. An algorithm for the diagnosis of hypokalemia of renal origin in pediatric population is presented here on the basis of values of blood pressure, circulating concentrations of aldosterone and renin and the status of acid-base equilibrium (AU)


Assuntos
Humanos , Masculino , Feminino , Criança , Hipopotassemia/fisiopatologia , Desequilíbrio Ácido-Base/fisiopatologia , Determinação da Pressão Arterial/métodos , Sistema Renina-Angiotensina/fisiologia , Renina/análise , Aldosterona/análise , Equilíbrio Ácido-Base/fisiologia
20.
Eur J Oral Sci ; 119(5): 345-51, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21896050

RESUMO

The renin-angiotensin system is thought to be involved in inflammatory processes such as periodontitis. However, its precise role is still unclear. Therefore, in the present study the expression of the angiotensin II type 1 receptor (AT1R) was investigated in inflamed human gingival tissue, and the possible involvement of the AT1R in interleukin-1ß (IL-1ß)-induced interleukin-6 (IL-6) production by cultured human gingival fibroblasts (HGFs) was also studied. Immunohistochemical staining revealed that inflammatory cells and fibroblast-like cells were positive for the AT1R. However, in healthy gingival tissue, AT1R staining was very weak. The levels of AT1R mRNA and AT1R protein increased in HGFs after stimulation with IL-1ß. The levels of IL-1ß-induced IL6 mRNA and IL-6 protein were significantly reduced in AT1R gene-silenced HGFs compared with control HGFs. The data suggest that the AT1R may be involved in the regulation of gingival inflammation by modulating IL-1ß-induced IL-6 production in HGFs.


Assuntos
Gengiva/metabolismo , Interleucina-1beta/farmacologia , Interleucina-6/análise , Receptor Tipo 1 de Angiotensina/efeitos dos fármacos , Angiotensinogênio/análise , Catepsina D/análise , Células Cultivadas , Regulação para Baixo , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Inativação Gênica , Gengiva/efeitos dos fármacos , Gengivite/metabolismo , Gengivite/patologia , Humanos , Interleucina-6/biossíntese , Peptidil Dipeptidase A/análise , RNA Interferente Pequeno/genética , Reação em Cadeia da Polimerase em Tempo Real , Receptor Tipo 1 de Angiotensina/análise , Receptor Tipo 1 de Angiotensina/genética , Renina/análise , Sistema Renina-Angiotensina/fisiologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa
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