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J. physiol. biochem ; 74(3): 467-478, ago. 2018. tab, graf, ilus
Artigo em Inglês | IBECS | ID: ibc-179000


Despite the effectiveness of renin-angiotensin blockade in retarding diabetic nephropathy progression, a considerable number of patients still develop end-stage renal disease. The present investigation aims to evaluate the protective potential of FPS-ZM1, a selective inhibitor of receptor for advanced glycation end products (RAGE), alone and in combination with valsartan, an angiotensin receptor blocker, against glomerular injury parameters in streptozotocin-induced diabetic rats. FPS-ZM1 at 1 mg/kg (i.p.), valsartan at 100 mg/kg (p.o.), and their combination were administered for 4 weeks, starting 2 months after diabetes induction in rats. Tests for kidney function, glomerular filtration barrier, and podocyte slit diaphragm integrities were performed. Combined FPS-ZM1/valsartan attenuated diabetes-induced elevations in renal levels of RAGE and phosphorylated NF-κB p65 subunit. It ameliorated glomerular injury due to diabetes by increasing glomerular nephrin and synaptopodin expressions, mitigating renal integrin-linked kinase (ILK) levels, and lowering urinary albumin, collagen type IV, and podocin excretions. FPS-ZM1 also improved renal function as demonstrated by decreasing levels of serum cystatin C. Additionally, the combination also alleviated indices of renal inflammation as revealed by decreased renal monocyte chemoattractant protein 1 (MCP-1) and chemokine (C-X-C motif) ligand 12 (CXCL12) expressions, F4/80-positive macrophages, glomerular TUNEL-positive cells, and urinary alpha-1-acid glycoprotein (AGP) levels. These findings underline the benefits of FPS-ZM1 added to valsartan in alleviating renal glomerular injury evoked by diabetes in streptozotocin rats and suggest FPS-ZM1 as a new potential adjunct to the conventional renin-angiotensin blockade

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Humanos , Masculino , Ratos , Benzamidas/uso terapêutico , Diabetes Mellitus Experimental/complicações , Nefropatias Diabéticas/prevenção & controle , Barreira de Filtração Glomerular , Valsartana/uso terapêutico , Insuficiência Renal/prevenção & controle , Administração Oral , Bloqueadores do Receptor Tipo 1 de Angiotensina II/administração & dosagem , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Biomarcadores , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/fisiopatologia , Barreira de Filtração Glomerular/metabolismo , Barreira de Filtração Glomerular/patologia , Valsartana/administração & dosagem
Aten. prim. (Barc., Ed. impr.) ; 49(3): 150-155, mar. 2017. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-161271


OBJETIVO: Analizar el efecto de una intervención para reducir el riesgo de iatrogenia asociada a prescripciones crónicas concomitantes de inhibidores de la enzima de conversión de angiotensina (iECA) y/o antagonistas del receptor de la angiotensina II (ARA-II) con diuréticos y antiinflamatorios no esteroideos (AINE), combinación denominada triple whammy (TW). DISEÑO: Estudio de intervención antes-después. Emplazamiento: Quince centros de salud de un sector sanitario (población de referencia de 292.746 pacientes). PARTICIPANTES: Un total de 260 pacientes con edad ≥18 años y prescripciones crónicas concomitantes de fármacos de los grupos terapéuticos (código ATC): diuréticos (C03), iECA/ARA-II (C09) y AINE (M01), en enero de 2015. INTERVENCIONES: Intervención doble durante febrero y marzo de 2015: educacional (sesión informativa) e individualizada (revisión de historias clínicas y recomendaciones al médico de cabecera). Mediciones principales: Se analizó el número de pacientes en los que se aceptó al menos una recomendación y el número de pacientes que continuaban con la combinación TW prescrita en junio de 2015. Se analizaron los datos mediante estadística descriptiva y se comparó la prevalencia de TW en junio de 2015 con la inicial mediante método híbrido de Newcombe-Wilson. RESULTADOS: Se incluyeron 260 pacientes. En 165 (63,5%) se realizó alguna recomendación, y en 97 (58,8%) se aceptó al menos una. En junio de 2015, 184 pacientes continuaban con la combinación TW. La prevalencia de TW tras la intervención disminuyó en 0,19/1.000 pacientes (IC 95%: 0,04/1.000 a 0,34/1.000; p = 0,017). CONCLUSIONES: La intervención realizada mejoró la prescripción y redujo el número de pacientes con la combinación TW

OBJECTIVE: To analyze the effect of an intervention to reduce the iatrogenic risk associated with concomitant treatment with angiotensin converting enzyme inhibitors (ACEi) and/or angiotensin-II receptor blockers (ARB) with diuretics and nonsteroidal anti-inflamatory drugs (NSAID), combination known as triple whammy (TW). DESIGN: Uncontrolled before-after intervention study. LOCATION: 15 health centers from a health area (reference population of 292.746 habitants). PARTICIPANTS: 260 patients ≥18 years old with chronic and concomitant prescriptions of drugs from the therapeutic groups (ATC code): diuretics (C03), ACEi/ARBs (C09) and NSAID (M01) during the month of January 2015. INTERVENTIONS: A double intervention was conducted during February and March 2015: an educational part, which consisted of an informative session, and an individualized part, in which recommendations to general practitioner were assessed after reviewing medical records. MAIN MEASUREMENTS: The number of patients in whom at least one intervention was accepted and the number of patients who continued on TW combination in June 2015, were analyzed. Results were analyzed using descriptive statistics and the prevalence of TW was compared with the one in June 2015 using the Newcombe-Wilson's hybrid method. RESULTS: 260 patients were included in the study. Recommendations were made in 165 patients (63.5%) and at least one was accepted in 97 (58.8%) patients. In June 2015, 184 patients continued with the TW combination. The TW prevalence decreased by 0.19/1,000 patients (IC 95%: 0.04/1,000 to 0.34/1,000; P=0.017) after the intervention. CONCLUSIONS: The intervention improved the prescription and reduced the number of patients on TW combination

Humanos , /uso terapêutico , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Lesão Renal Aguda/prevenção & controle , Avaliação de Resultado de Intervenções Terapêuticas , Doença Iatrogênica/prevenção & controle , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/prevenção & controle , Diuréticos/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Interações Medicamentosas
J. physiol. biochem ; 72(4): 813-820, dic. 2016. graf, ilus
Artigo em Inglês | IBECS | ID: ibc-168386


Many studies demonstrated that angiotensin 2 type 1 receptor (AT1R) blockade accelerates renal recovery in post-ischaemic kidney but there are many controversies related to its net effect on kidney structure and function. During the past years, our research group was trying to define the pathophysiological significance of the renin-angiotensin system on post-ischemic acute renal failure (ARF) development in normotensive Wistar as well as hypertensive rats (SHR). This review mostly summarizes our experience in that field. Our previous studies in normotensive rats revealed that AT1R blockade, except slightly renal vascular resistance improvement, had no other obvious beneficial effects, and therefore implies angiotensin 2 (Ang-2) overexpression as non-dominant on kidney reperfusion injuries development. Similarly it was observed in Wistar rats with induced mild (L-NAME, 3 mg/kg b.w.) nitric oxide (NO) deficiency. Expectably, in strong induced (L-NAME, 10 mg/kg b.w.) NO deficiency associated with ARF, massive tubular injuries indicate harmful effects of AT1R blockade, implying strongly disturbed glomerular filtration and suggesting special precaution related to AT1R blockers usage. Opposite to previous, by our opinion, AT1R antagonism promises new advance in treatment of essentially hypertensive subjects who develop ARF. Increased glomerular filtration, diminished oxidative stress, and most importantly improved tubular structure in postishemic SHR treated with AT1R blocker losartan, implicate Ang-2 over production as potently agent in the kidney ischemic injury, partly trough generation of reactive oxygen species. These data contribute understanding the pathogenesis of this devastating illness in hypertensive surroundings (AU)

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Animais , Ratos , Lesão Renal Aguda/tratamento farmacológico , Hipertensão/tratamento farmacológico , Rim , Losartan/farmacologia , Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Traumatismo por Reperfusão/tratamento farmacológico , Regulação da Expressão Gênica , Taxa de Filtração Glomerular , Óxido Nítrico/metabolismo , Sistema Renina-Angiotensina , Espécies Reativas de Oxigênio/metabolismo , Receptor Tipo 1 de Angiotensina , Resistência Vascular , Artéria Renal
Rev. esp. cardiol. Supl. (Ed. impresa) ; 15(supl.E): 12e-18e, 2015. graf, tab
Artigo em Espanhol | IBECS | ID: ibc-165829


En prevención secundaria cardiovascular, el grado de control de los factores de riesgo cardiovascular es deficiente en los países europeos y la falta de adherencia terapéutica parece ser uno de los factores causales. La buena adherencia se asocia a un 20% de disminución del riesgo de enfermedad cardiovascular y un 38% de disminución de mortalidad por cualquier causa. Los pacientes con mala adherencia multiplican por 3 el riesgo de mortalidad. Sin embargo, la adherencia a los fármacos preventivos (ácido acetilsalicílico, bloqueadores beta, inhibidores de la enzima de conversión de la angiotensina, estatinas, etc.) ronda el 50% 1 año después del alta hospitalaria. La Organización Mundial de la Salud define adherencia terapéutica como el grado en que el comportamiento de una persona, con respecto a tomar la medicación o seguir una recomendación dietética o de cambio de estilo de vida, concuerda con las prescripciones del profesional sanitario consensuadas con el paciente. No existe un método ideal para medir la adherencia, pero se recomienda para la práctica clínica la pregunta de Haynes-Sackett y el cuestionario de Morisky-Green de ocho ítems. No obstante, el patrón de referencia sigue siendo el recuento de comprimidos, y se considera buena adherencia el consumo de más del 80% de la prescripción. Mejorar la comunicación entre médicos y pacientes, facilitar la continuidad asistencial mediante la colaboración con atención primaria, involucrar a otros profesionales sanitarios (farmacéuticos) y el desarrollo de terapias combinadas a dosis fijas, como la polypill, son estrategias que pueden mejorar la adherencia terapéutica y el grado de control y reducir los costes sanitarios (AU)

In secondary cardiovascular prevention, the degree of control of cardiovascular risk factors in European countries is inadequate and poor treatment adherence appears to be one of the causative factors. Good adherence has been associated with a 20% reduction in the risk of cardiovascular disease and a 38% decrease in all-cause mortality. Patients with poor adherence have a three-fold increased risk of death. However, adherence to treatment involving preventive drugs (e.g. aspirin, beta-blockers, angiotensinconverting enzyme inhibitors and statins) is only around 50% 1 year after hospital discharge. The World Health Organization defines treatment adherence as the degree to which an individual’s behavior with respect to taking medications or implementing recommended dietary or lifestyle changes corresponds with the actions health-care professionals have agreed with the patient. There is no ideal way of measuring adherence but it is recommended that the Haynes-Sackett test and the Morisky-Green 8-item questionnaire should be used in clinical practice. Nevertheless, the reference standard remains the pill count, with good adherence being considered an intake more than 80% of that prescribed. Strategies for ensuring better treatment adherence, increasing the degree of disease control and reducing health-care costs include improving communication between doctors and patients, facilitating the continuity of care by collaborating with primary care staff, involving other health-care professionals (e.g. pharmacists) and developing fixed-dose combination therapies, such as the polypill (AU)

Humanos , Isquemia Miocárdica/tratamento farmacológico , /uso terapêutico , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Adesão à Medicação/estatística & dados numéricos , Intervalo Livre de Doença , Fatores de Risco , Isquemia Miocárdica/prevenção & controle , Combinação de Medicamentos , Custos de Cuidados de Saúde , Anti-Hipertensivos/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Aspirina/uso terapêutico
Nutr. hosp ; 27(1): 276-280, ene.-feb. 2012.
Artigo em Espanhol | IBECS | ID: ibc-104884


Introducción: El telmisartan es un ARA II con unas características propias que nos permite obtener unos beneficios adicionales. Además de bloquear el receptor I de la angiotensina II, va actuar a través de receptores nucleares claves como el receptor PPARgamma. Por otra parte, PPARgamma interviene en el control del remodelado óseo aunque con resultados no concordantes. El objetivo del presente estudio es valorar el efecto de telmisartan sobre marcadores del remodelado óseo en población hipertensa. 
Pacientes y métodos: Se evaluaron pacientes 31 hipertensos de edad superior a 45 años sin otras patologías asociadas. La dosis de telmisartan fue de 80 mg/24 h y el periodo de seguimiento fue de 12 semanas. Como grupo control empleamos una cohorte histórica de pacientes tratados previamente con IECA (enalapril-20 mg/24 h-o quinapril-40 mg/24 horas). Se determinaron los siguientes parámetros P1NP, β-CTX, 25OHD y PTH, adiponectina , osteocalcina , insulina y HOMA. Resultados: Los pacientes tratados con Telmisartan descienden los niveles de TAS (156 ± 19 mmHg vs 133 ± 15 mmHg, p = 0,001 ) y TAD (92 ± 9 mmHg vs 82 ± 6 mmHg, p = 0,01) de forma estadísticamente significativa. No se observaron cambios en los parámetros de metabolismo fosfocálcico, PTHi (48 ± 22 pg/ml vs 45 ± 22 pg/ml, p > 0,05) y 25-vitamina D (21 ± 10 ng/ml vs 25 ± 8 ng/ml, p > 0,05). El telmisartan no modifico los marcadores del remodelado óseo siendo su efecto neutro sobre los mismos, CTX (0,195 ± 0,12 ng/ml vs 0,221 ± 0,13 ng/ml, p > 0,05), PINP (39 ± 20 ng/ml vs 40 ± 19 ng/ml, p > 0,05), Osteocalcina (11 ± 9 ng/ml vs 11 ± 5 ng/ml, p > 0,05 ). Tampoco se observaron variaciones en los niveles de glucosa, adiponectina, insulina e indice de Resistencia a la Insulina (HOMA). Al dividir los pacientes en dos grupos en función de los niveles de vitamina D (insuficientes y no insuficientes), con un punto de corte de 20 ng/ml, tampoco se modificaron los marcadores del remodelado aunque se observó un descenso de la glucosa en pacientes con niveles de vitamina D por encima de 20 ng/ml (135 ± 53 mg/dl vs 119 ± 39 mg/dl, p = 0,01). Los pacientes tratados con IECAS disminuyen los valores de tensión arterial sistólica pero la diastólica no muestra cambios. Conclusiones: Telmisartan tiene un efecto neutro a nivel de los marcadores del remodelado óseo (AU)

Introduction: The telmisartan is an angiotensin II receptor blocker (ARB) with a few own characteristics that it allows us to obtain a few additional benefits. It displays the ability to act as a partial agonist of PPARgamma. On the other hand, PPAR gamma intervenes in the control of bone remodelling though with not concordant results. The objective of this study to value the effect of telmisartan on bone markers in hypertensive patients. Subjects: A sample of 31 hypertensive patients with hypertension were included. The dose of telmisartan was of 80 mg/24 h and the period of follow-up was 12 weeks. The control group included 32 hypertensive patients treated before with IECA (enalapril-20 mg/24 h - or quinapril - 40 mg/24 hours). The following parameters were determined P1NP, β-CTX, 25OHD and PTH , osteocalcin, insulin and adiponectin. Results: The patients treated with Telmisartan shown a significantly decrease in systolic blood pressure (156 ± 19 mmHg vs 133 ± 15 mmHg, p = 0.001) and diastolic blood pressure (92 ± 9 mmHgvs 82 ± 6 mmHg, p = 0.01) . Changes were not observed in other parameter, PTHi (48 ± 22 pg/ml vs 45 ± 22 pg/ml, p > 0.05) and 25-vitamin D (21 ± 10 ng/ml vs 25 ± 8 ng/ml, p > 0.05), CTX (0.195 ± 0.12 ng/ml vs 0.221 ± 0.13 ng/ml, p > 0.05), PINP (39 ± 20 ng/ml vs 40 ± 19 ng/ml, p > 0.05), osteocalcin (11 ± 9 ng/ml vs 11 ± 5 ng/ml, p > 0.05), glucose, adiponectin, insulin and HOMA. When the patients divided in two groups depending on the levels of vitamin D (insufficient and not insufficient), with a cut of 20 ng/ml, there was changes on bone markers but a decrease of the glucose was observed in patients with levels of vitamin D over 20 ng/ml (135 ± 53 mg/dl vs 119 ± 39 mg/dl, p = 0.01). The patients treated with IECAS decreases the systolic blood pressure but the diastolic blood pressure values of arterial systolic does not show changes. Conclusions: Telmisartan has a neutral effect to level of the bone markers of bone remodelling (AU)

Humanos , Hipertensão/tratamento farmacológico , Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacocinética , Remodelação Óssea , Anti-Hipertensivos/farmacocinética , PPAR gama
Sanid. mil ; 67(4): 369-371, oct.-dic. 2011.
Artigo em Espanhol | IBECS | ID: ibc-98005


Se reseñan los medicamentos ya evaluados por la Agencia Española de Medicamentos y Productos Sanitarios hechos públicos en el tercer trimestre de 2011, y considerados de mayor interés para el profesional sanitario en el ámbito hospitalario. Se trata de opiniones técnicas positivas que son previas a la autorización y puesta en el mercado del medicamento (AU)

The drugs assessed by the Spanish Agency for Medicines and Health Products made public in the third quarter of 2011, and considered of interest in hospital healthcare professional, are reviewed. These are positive technical reports prior to the authorization and placing on the market of the product (AU)

Humanos , Drogas em Investigação , Antivirais/farmacologia , Antibacterianos/farmacologia , Hipoglicemiantes/farmacologia , Inibidores da Transcriptase Reversa/farmacologia , Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Antagonistas de Androgênios/farmacologia
Rev. esp. cardiol. Supl. (Ed. impresa) ; 11(supl.D): 3d-7d, 2011. graf, tab
Artigo em Espanhol | IBECS | ID: ibc-166480


La renina es la enzima encargada de transformar el angiotensinógeno en angiotensina I, primer paso en la activación del sistema renina-angiotensina (SRA). La actividad de la renina plasmática (ARP) mide la capacidad de la renina para producir angiotensina I a partir de angiotensinógeno, se expresa como concentración de angiotensina I generada por unidad de tiempo (ng/ml/h) y se utiliza para valorar el grado de activación del SRA. Hay relación entre valores de ARP y enfermedad cardiovascular. Se ha descrito que valores de ARP alta se asocian con mayor incidencia de infarto agudo de miocardio, pérdida de función renal, peor pronóstico de la insuficiencia cardiaca y aumento de la mortalidad por causa cardiovascular. La inhibición del SRA con fármacos inhibidores de la enzima de conversión de la angiotensina o con antagonistas del receptor de la angiotensina incrementa la secreción de renina, y por lo tanto la ARP, como consecuencia de la interrupción del mecanismo de retroalimentación negativa que regula la secreción de renina a partir de las concentraciones de angiotensina II. Sin embargo, los inhibidores directos de la renina, como el aliskiren, aunque también interrumpen el mecanismo de retroalimentación y aumentan la secreción de renina, disminuyen la ARP porque bloquean su actividad catalítica. Esta característica diferencial de los inhibidores directos de la renina puede conferirles ventajas en cuanto a la reducción del riesgo cardiovascular (AU)

Renin is the enzyme responsible for the conversion of angiotensinogen into angiotensin I, the first step in the activation of the renin-angiotensin system (RAS). Plasma renin activity (PRA) provides a measure of the capacity of renin to produce angiotensin I from angiotensinogen and is expressed as the rate of increase in the angiotensin-I concentration (i.e. ng/mL per hour). The PRA level is used to evaluate the degree of activation of the RAS. There is a relationship between the PRA level and cardiovascular disease. It has been reported that a high PRA level is associated with an increased incidence of myocardial infarction, with the loss of kidney function, with a poor prognosis in patients with heart failure, and with increased mortality due to cardiovascular causes. Inhibition of the RAS by angiotensin-converting enzyme inhibitors and angiotensin-receptor antagonists increases renin secretion and, thereby, increases the PRA level. This is due to interruption of negative feedback mechanism that regulates renin secretion in accordance with the angiotensin-II concentration. However, direct renin inhibitors such as aliskiren, although they also interrupt the feedback mechanism and increase renin secretion, reduce PRA by blocking renin’s catalytic activity. This distinctive property of direct renin inhibitors could be advantageous in helping to reduce cardiovascular risk (AU)

Humanos , Cardiotônicos/farmacocinética , Doenças Cardiovasculares/prevenção & controle , Renina/antagonistas & inibidores , Renina/sangue , Sistema Renina-Angiotensina , Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacocinética , /farmacocinética
Rev. esp. cardiol. Supl. (Ed. impresa) ; 11(supl.D): 8d-12d, 2011. ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-166481


El reciente descubrimiento de un receptor de (pro-)renina, al que se unen pro-renina y renina, ha renovado el interés por la pro-renina. Esta es el precursor de la renina sintetizada en el aparato yuxtaglomerular y se produce también extrarrenalmente. En situaciones clínicas como la diabetes, hay valores elevados de prorenina en plasma que se asocian a daño microvascular. Tras unirse al receptor, la pro-renina experimenta una activación no proteolítica que consiste en la separación del prosegmento, lo que le confiere capacidad catalítica para generar angiotensina I a partir del angiotensinógeno. Por otra parte, la unión de (pro-)renina al receptor induce la activación de cinasas que intervienen en la diferenciación celular (neuronal) y en la formación de citocinas fibrogénicas y otros mediadores de lesión tisular. Además de ejercer efectos relacionados con el sistema renina-angiotensina-aldosterona (SRAA), el receptor (pro-)renina se une a la ATPasa vacuolada, implicada en la acidificación intracelular y en otras importantes funciones para la viabilidad celular. El uso de un péptido similar a una parte del prosegmento de la pro-renina que impide la unión de pro-renina al receptor ha dado resultados discrepantes en modelos experimentales. En algunos casos, ha sido eficaz para prevenir o atenuar la nefropatía diabética y la fibrosis cardiaca y en otros no. Los inhibidores directos de la renina (IDR) tienen capacidad de unirse a la (pro-)renina ligada al receptor e impedir su acción catalítica. La mayoría de los estudios no evidencian la capacidad de los IDR para suprimir los efectos no catalíticos (no dependientes de la angiotensina II) del complejo (pro-)renina-receptor. Todavía hay muchos interrogantes sobre el papel de la pro-renina en la generación tisular e intracelular de la angiotensina II, los efectos intracelulares inducidos por la unión pro-renina-receptor y sobre la relevancia de la función del receptor (pro-)renina no relacionado con el SRA. Asimismo, surgen muchas cuestiones sobre posibles agentes que bloqueen el receptor (pro-)renina y sobre el efecto de los IDR en las consecuencias celulares, dependientes e independientes de la angiotensina II, de la interacción (pro-)renina-receptor (AU)

The recent discovery of a (pro)renin receptor that binds both prorenin and renin has renewed interest in prorenin. Prorenin is the precursor of renin and is synthesized mainly in the juxtaglomerular apparatus, although it is also produced outside the kidney. In clinical conditions such as diabetes mellitus, high plasma levels of prorenin are observed to occur in association with microvascular damage. After binding to its receptor, prorenin undergoes nonproteolytic activation, which involves separation of the prosegment. Through this process the molecule acquires the ability to catalyze the production of angiotensin I from angiotensinogen. On the other hand, the binding of (pro)renin to its receptor induces the activation of a number of kinases involved in the differentiation of neuronal cells and in the production of fibrogenic cytokines and other mediators of tissue damage. As well as having an effect on the renin-angiotensinaldosterone system (RAAS), the (pro)renin receptor binds to vacuolar ATPase, which is involved in intracellular acidification and other processes vital for cell viability. Experimental studies with a synthetic peptide which is similar to part of the prorenin prosegment and which prevents prorenin binding with its receptor have produced conflicting findings. In some cases, the peptide has been effective in preventing or reducing diabetic nephropathy and cardiac fibrosis, while in others it has not. Direct renin inhibitors (DRIs) are able to bind to receptor-bound (pro)renin, thereby blocking its catalytic activity. Most studies have found no evidence that DRIs are able to suppress the noncatalytic (i.e. non-angiotensin-II-dependent) effects of the (pro)renin-receptor complex. There are still many unanswered questions about the role of prorenin in the production of both tissular and intracellular angiotensin II, about the intracellular effects induced by the binding of prorenin to its receptor, and about the importance of the (pro)renin receptor beyond its effect on the RAAS. Similarly, many questions have arisen about drugs that can block the (pro)renin receptor and about the effect of DRIs on the cellular implications of the interaction between (pro)renin and its receptor, whether dependent on or independent of angiotensin II (AU)

Humanos , Renina/antagonistas & inibidores , /farmacocinética , Doenças Cardiovasculares/prevenção & controle , Sistema Renina-Angiotensina , Receptores de Angiotensina , Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacocinética
Rev. esp. cardiol. Supl. (Ed. impresa) ; 11(supl.D): 18d-24d, 2011. graf, tab
Artigo em Espanhol | IBECS | ID: ibc-166483


El bloqueo a distintos niveles del sistema renina-angiotensina ha demostrado importantes beneficios en la reducción de la morbimortalidad cardiovascular. La introducción en el arsenal terapéutico del aliskiren, un inhibidor directo de la renina, ha abierto una nueva vía para el tratamiento de la hipertensión y la protección de los órganos diana. El aliskiren tiene una eficacia antihipertensiva similar a la de otros fármacos antihipertensivos, con un perfil de seguridad y tolerabilidad comparable al del placebo, incluido el tratamiento de hipertensos diabéticos obesos y pacientes de edad avanzada, con reducción persistente de la presión arterial y una supresión prolongada de la activación de renina plasmática, incluso tras la retirada del fármaco. Los datos disponibles de diferentes estudios clínicos y experimentales indican que el aliskiren es capaz de proteger contra el daño de los órganos diana, especialmente en pacientes diabéticos. Los prometedores resultados de los ensayos clínicos realizados con aliskiren en pacientes hipertensos, que evalúan marcadores de daño orgánico renal y cardiaco, refrendan la importancia de inhibir el sistema renina-angiotensina-aldosterona cuando se busca reducir la morbimortalidad cardiovascular y renal. El actual programa de ensayos clínicos ASPIRE HIGHER está diseñado para evaluar indirecta (acciones sobre diferentes marcadores) y directamente (efectos en diferentes órganos diana) la capacidad organoprotectora del aliskiren; los resultados que se obtengan definirán el papel de la inhibición directa de la renina en el tratamiento de la hipertensión arterial y, sobre todo, en la reducción de la morbimortalidad cardiovascular (AU)

Blockade of different levels of the renin-angiotensin system has produced substantial benefits in terms of reducing cardiovascular morbidity and mortality. The introduction of aliskiren, a direct renin inhibitor, into the therapeutic arsenal has provided a new way of treating hypertension and protecting target organs. The antihypertensive efficacy of aliskiren is similar to that of other antihypertensive drugs and its safety and tolerability profiles are similar to those of placebo, even when used to treat obese hypertensive diabetics and elderly patients. Its use results in a persistent reduction in blood pressure and prolonged suppression of plasma renin activity, even after drug withdrawal. Data available from various clinical and preclinical studies indicate that aliskiren is capable of protecting against target organ damage, especially in diabetics. The promising results of clinical trials of aliskiren in hypertensive patients, which have looked at markers of organ damage in the kidneys and heart, confirm the importance of inhibiting the renin-angiotensinaldosterone system when seeking to reduce cardiovascular and renal morbidity and mortality. The current ASPIRE HIGHER clinical trial program was designed to evaluate, both indirectly (via effects on various markers) and directly (via effects on target organs), the ability of aliskiren to protect against organ damage. The results obtained will determine the role that direct renin inhibition can play in the treatment of arterial hypertension and, above all, in reducing cardiovascular morbidity and mortality (AU)

Humanos , Hipertrofia Ventricular Esquerda/prevenção & controle , Nefropatias Diabéticas/prevenção & controle , Hipertensão/prevenção & controle , Anti-Hipertensivos/farmacocinética , Renina/antagonistas & inibidores , Fatores de Proteção , /farmacocinética , Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacocinética , Doenças Cardiovasculares/prevenção & controle
Rev. esp. cardiol. Supl. (Ed. impresa) ; 11(supl.D): 37d-41d, 2011. ilus, graf
Artigo em Espanhol | IBECS | ID: ibc-166485


El sistema renina-angiotensina desempeña un papel determinante en la aparición de complicaciones cardiovasculares y renales en el contexto de la diabetes mellitus. Las acciones del sistema renina-angiotensina incluyen no sólo las dependientes de la producción de angiotensina II, sino también las resultantes de la activación del sistema renina-pro-renina/receptor de la pro-renina. En los últimos años, diversos estudios clínicos y experimentales señalan la implicación del sistema renina-pro-renina/receptor de la pro-renina en el daño de órganos diana en la diabetes mellitus. Este artículo revisa los principales estudios que han contribuido a una mayor comprensión de dicho sistema y de su papel como posible diana terapéutica en la diabetes mellitus (AU)

The renin-angiotensin system is a key determinant of the appearance of cardiovascular and renal complications in patients with diabetes mellitus. The actions of the renin-angiotensin system include not only those dependent on the production of angiotensin II but also those that result from activation of the renin-prorenin/prorenin-receptor system. In recent years, a range of clinical and experimental studies have indicated that the renin-prorenin/prorenin-receptor system is involved in target organ damage in diabetes mellitus. This paper contains a review of the main studies that have contributed to a better understanding of this system and its potential role as a therapeutic target in diabetes mellitus (AU)

Humanos , Sistema Renina-Angiotensina/fisiologia , Diabetes Mellitus/fisiopatologia , Complicações do Diabetes/fisiopatologia , Angiopatias Diabéticas/fisiopatologia , Nefropatias Diabéticas/fisiopatologia , /farmacocinética , Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacocinética