Dolor, calidad de vida y salud mental en pacientes con gonalgia por gonartrosis: estudio de casos y controles / Pain, quality of life and mental health in patients with gonalgia due to gonarthrosis: Cases and controls study

Objetivo: Evaluar el dolor, la calidad de vida y el estado psicológico en pacientes con gonalgia por gonartrosis. Material y métodos: Estudio epidemiológico, multicéntrico, de casos y controles. Se incluyeron 1.152 pacientes (576 con artrosis y 576 sin artrosis) apareados por edad y sexo, procedentes de 63 centros de salud de España. Se les administró la escala visual analógica de dolor de Huskisson y los cuestionarios EuroQol y Goldberg. Se realizó un análisis descriptivo y comparativo de los datos en ambos grupos. Se estudiaron los factores que influían en la CV y salud mental de los pacientes artrósicos con modelos de regresión logística. Resultados: Se incluyeron 576 pacientes casos y 576 controles. El 70,3% eran mujeres en ambos grupos. La puntuación media en la escala visual analógica de los artrósicos fue 65,2±4,9mm correspondiente a una intensidad moderada. El cuestionario EuroQol indicó peor estado de salud (p<0,05) en los pacientes con artrosis en todas sus dimensiones. El cuestionario Goldberg mostró la presencia de psicopatología en el 36,5% (n=209) de los casos, frente a un 14,0% (n=80) en los controles (p<0,001). El dolor fue la variable que afectó a la CV en todas las dimensiones (p<0,001). Conclusiones: Los pacientes con artrosis manifiestan dolor moderado, limitación de la movilidad, del cuidado personal y de las actividades cotidianas que repercute negativamente en su CV y psicológicamente se encuentran más afectados. Es prioritario desarrollar estrategias de autocuidado y tratamiento en estos pacientes para mejorar globalmente su CV (AU)

Objective: To evaluate pain, quality of life and psychological state in patients with gonalgia due to gonarthrosis. Material and methods: Epidemiological, multicenter, case–control study. 1.152 patients were included (576 with arthrosis and 576 without arthrosis) matched by age and sex, from 63 health centers in Spain. The Huskisson Pain Scale (VAS), the EuroQol and Goldberg questionnaires were administered. A descriptive and comparative analysis of the data was carried out in both groups. Factors influencing the quality of life and mental health of arthritic patientes were studied with logistic regression models. Results: 576 case patients and 576 controls were included. 70.3% were women in both groups. The mean score in the VAS score of the arthritic patients was 65±4.9mm corresponding to a moderate intensity. The EQ-5D questionnaire indicated a worse state of health (P<.05) in patients with osteoarthritis in each of its dimensions. In the GHQ-12 questionnaire, the presence of psychopathology was detected in 36.5% (n=209) of patients with osteoarthritis compared to 14.0% (n=80) in controls (P<.001). Pain was the variable that affected quality of life in all dimensions (P<.001). Conclusions: Patients with arthrosis manifest moderate pain due to this disease. They present a limitation of mobility, personal care and daily activities that negatively affects their quality of life and psychologically they are more affected. It is a priority to develop self-care and treatment strategies in this group of subjects to globally improve their quality of life (AU)

[Pain, quality of life and mental health in patients with gonalgia due to gonarthrosis: Cases and controls study]. / Dolor, calidad de vida y salud mental en pacientes con gonalgia por gonartrosis: estudio de casos y controles.

OBJECTIVE: To evaluate pain, quality of life and psychological state in patients with gonalgia due to gonarthrosis. MATERIAL AND METHODS: Epidemiological, multicenter, case-control study. 1.152 patients were included (576 with arthrosis and 576 without arthrosis) matched by age and sex, from 63 health centers in Spain. The Huskisson Pain Scale (VAS), the EuroQol and Goldberg questionnaires were administered. A descriptive and comparative analysis of the data was carried out in both groups. Factors influencing the quality of life and mental health of arthritic patientes were studied with logistic regression models. RESULTS: 576 case patients and 576 controls were included. 70.3% were women in both groups. The mean score in the VAS score of the arthritic patients was 65±4.9mm corresponding to a moderate intensity. The EQ-5D questionnaire indicated a worse state of health (P<.05) in patients with osteoarthritis in each of its dimensions. In the GHQ-12 questionnaire, the presence of psychopathology was detected in 36.5% (n=209) of patients with osteoarthritis compared to 14.0% (n=80) in controls (P<.001). Pain was the variable that affected quality of life in all dimensions (P<.001). CONCLUSIONS: Patients with arthrosis manifest moderate pain due to this disease. They present a limitation of mobility, personal care and daily activities that negatively affects their quality of life and psychologically they are more affected. It is a priority to develop self-care and treatment strategies in this group of subjects to globally improve their quality of life.

Mortalidad de una cohorte de hombres con fractura de cadera por fragilidad en un sector sanitario: factores asociados / Mortality in a cohort of men with fragility hip fracture in a health area: associated factors

FUNDAMENTOS: Una cuarta parte de los pacientes con fractura de cadera por fragilidad (FCF) son hombres, y estos presentan una mortalidad mayor que las mujeres. El objetivo de este trabajo es estudiar la mortalidad consecuencia de la FCF en hombres ≥65años, tanto intrahospitalaria como al año y a los 3años, y los posibles factores asociados. MATERIAL Y MÉTODOS: Estudio observacional analítico de una cohorte histórica de 182 pacientes varones con FCF ≥65años ingresados en un servicio de Cirugía Ortopédica y Traumatología (COT) entre enero de 2009 y diciembre de 2014. RESULTADOS: La mortalidad intrahospitalaria fue del 10,9% (6% en el servicio COT y 8,6% en el centro sociosanitario). Se encontró asociación entre la mortalidad intrahospitalaria y la edad (p = 0,039). Veinte pacientes murieron durante su estancia en ambos hospitales. Cuarenta y dos (25,9%) murieron un año después y 95 (58,6%) murieron 3años después. La demencia/deterioro cognitivo se relacionó con un riesgo relativo de mortalidad a un año de 2,2, y de mortalidad a 3años de 1,6. Encontramos asociación entre la edad y la mortalidad y entre el índice de Barthel al inicio y la mortalidad en ambos períodos. Las causas más frecuentes de muerte fueron cardiovasculares (15,7%) y tumores (13,6%). CONCLUSIONES: Los varones con FCF presentaron una mortalidad elevada tanto intrahospitalaria, como al año y a los 3años. El factor de riesgo más determinante de mortalidad al año es la demencia/deterioro cognitivo, y el de mortalidad a los 3años, la HTA

BACKGROUND: A quarter of the patients with fragility hip fracture (FHF) are men, and they have higher mortality rates than women. The objective of this study is to analyse the mortality, as well as associated factors, due to FHF in men aged ≥65years, while in hospital and at one and three years of follow-up. MATERIAL AND METHODS: An analytical observational study was conducted on a historical cohort of 182 male patients equal or older than 65 years that were admitted to an Orthopaedic Surgery and Traumatology (OST) Department between January 2009 and December 2014. RESULTS: Within-hospital mortality was 10.9% (6% in the OST Department, and 8.6% in a Social-Health centre). A relationship (P=.039) was found between within-hospital mortality and age. A total of 20 patients died during their stay in both units, 42 (25.9%) died one year later, and 95 (58.6%) died three years later. Dementia/cognitive impairment was associated with a relative risk of one-year mortality of 2.2, and 1.6 of three-year mortality. An association was observed between age and mortality and between Barthel Index at baseline and mortality at both periods. The most frequent causes of death were cardiovascular (15.7%) and tumours (13.6%). CONCLUSIONS: Male patients with FHF showed high mortality rates in hospital, and at one-year and three-years follow-up. The most important risk factor of mortality was dementia/cognitive deterioration at one year, and high blood pressure at three years

[Mortality in a cohort of men with fragility hip fracture in a health area: Associated factors]. / Mortalidad de una cohorte de hombres con fractura de cadera por fragilidad en un sector sanitario: factores asociados.

BACKGROUND: A quarter of the patients with fragility hip fracture (FHF) are men, and they have higher mortality rates than women. The objective of this study is to analyse the mortality, as well as associated factors, due to FHF in men aged ≥65years, while in hospital and at one and three years of follow-up. MATERIAL AND METHODS: An analytical observational study was conducted on a historical cohort of 182 male patients equal or older than 65 years that were admitted to an Orthopaedic Surgery and Traumatology (OST) Department between January 2009 and December 2014. RESULTS: Within-hospital mortality was 10.9% (6% in the OST Department, and 8.6% in a Social-Health centre). A relationship (P=.039) was found between within-hospital mortality and age. A total of 20 patients died during their stay in both units, 42 (25.9%) died one year later, and 95 (58.6%) died three years later. Dementia/cognitive impairment was associated with a relative risk of one-year mortality of 2.2, and 1.6 of three-year mortality. An association was observed between age and mortality and between Barthel Index at baseline and mortality at both periods. The most frequent causes of death were cardiovascular (15.7%) and tumours (13.6%). CONCLUSIONS: Male patients with FHF showed high mortality rates in hospital, and at one-year and three-years follow-up. The most important risk factor of mortality was dementia/cognitive deterioration at one year, and high blood pressure at three years.

Prognostic factors in neoadjuvant treatment followed by surgery in stage IIIA-N2 non-small cell lung cancer: a multi-institutional study by the Oncologic Group for the Study of Lung Cancer (Spanish Radiation Oncology Society).

PURPOSE: To evaluate the prognostic factors associated with survival in patients treated with neoadjuvant treatment [chemoradiotherapy (CRT) or chemotherapy] followed by surgery (CRTS) in patients with stage IIIA-N2 non-small cell lung cancer (NSCLC). METHODS: A retrospective study was conducted of 118 patients diagnosed with stage T1-T3N2M0 NSCLC and treated with CRTS at 14 hospitals in Spain between January 2005 and December 2014. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method and compared using the log-rank test. Cox regression analysis was performed. RESULTS: Surgery consisted of lobectomy (74.5% of cases), pneumectomy (17.8%), or bilobectomy (7.6%). Neoadjuvant treatment was CRT in 62 patients (52.5%) and chemotherapy alone in 56 patients (47.5%). Median follow-up was 42.5 months (5-128 months). 5-year OS and PFS were 51.1% and 49.4%, respectively. The following variables were independently associated with worse OS and PFS: pneumonectomy (vs. lobectomy); advanced pathologic T stage (pT3 vs. pT0-pT2); and presence of persistent N2 disease (vs. ypN0-1) in the surgical specimen. CONCLUSIONS: In this sample of patients with stage IIIA-N2 NSCLC treated with CRTS, 5-year survival (both OS and PFS) was approximately 50%. After CRTS, the patients with the best prognosis were those whose primary tumour and/or mediastinal nodal metastases were downstaged after induction therapy and those who underwent lobectomy. These findings provide further support for neoadjuvant therapy followed by surgery in selected patients.

Neoadjuvant treatment followed by surgery versus definitive chemoradiation in stage IIIA-N2 non-small-cell lung cancer: A multi-institutional study by the oncologic group for the study of lung cancer (Spanish Radiation Oncology Society).

OBJECTIVES: The role of surgery in stage IIIA-N2 non-small cell lung cancer (NSCLC) is an actively debated in oncology. To evaluate the value of surgery in this patient population, we conducted a multi-institutional retrospective study comparing neoadjuvant chemoradiotherapy or chemotherapy plus surgery (CRTS) to definitive chemoradiotherapy (dCRT). MATERIAL AND METHODS: A total of 247 patients with potentially resectable stage T1-T3N2M0 NSCLC treated with either CRTS or dCRT between January 2005 and December 2014 at 15 hospitals in Spain were identified. A centralized review was performed to ensure resectability. A propensity score matched analysis was carried out to balance patient and tumor characteristics (n = 78 per group). RESULTS: Of the 247 patients, 118 were treated with CRTS and 129 with dCRT. In the CRTS group, 62 patients (52.5%) received neoadjuvant CRT and 56 (47.4%) neoadjuvant chemotherapy. Surgery consisted of either lobectomy (97 patients; 82.2%) or pneumonectomy (21 patients; 17.8%). In the matched samples, median overall survival (OS; 56 vs 29 months, log-rank p = .002) and progression-free survival (PFS; 46 vs 15 months, log-rank p < 0.001) were significantly higher in the CRTS group. This survival advantage for CRTS was maintained in the subset comparison between the lobectomy subgroup versus dCRT (OS: 57 vs 29 months, p < 0.001; PFS: 46 vs 15 months, p < 0.001), but not in the comparison between the pneumonectomy subgroup and dCRT. CONCLUSION: The findings reported here indicate that neoadjuvant chemotherapy or chemoradiotherapy followed by surgery (preferably lobectomy) yields better OS and PFS than definitive chemoradiotherapy in patients with resectable stage IIIA-N2 NSCLC.

Effect of eplerenone on hypertension-associated renal damage in rats: potential role of peroxisome proliferator activated receptor gamma (PPAR-γ).

UNLABELLED: Several factors, including mineralocorticoids, have been implicated in the renal damage associated with hypertension. Peroxisome proliferator activated receptor gamma (PPAR-γ) agonists improve renal damage associated with different pathologies. Therefore, our hypothesis was that mineralocorticoid receptor blockade ameliorates renal damage associated with hypertension and that this improvement may be mediated by PPAR-γ. Spontaneously hypertensive rats (SHR) were treated with either vehicle or eplerenone, a mineralocorticoid receptor antagonist, at two different doses: 30 and 100 mg/kg/day for 10 weeks. Age-matched Wistar Kyoto rats (WKY) were used as a normotensive reference group. SHR showed tubulointersticial fibrosis and mild tubular atrophy. These alterations were accompanied by increases in renal cortex gene expression of transforming growth factor beta (TGF-ß) connective tissue growth factor (CTGF) and phosphorylated Smad2 protein levels, factors involved in the fibrotic response. Interleukin 1-beta (IL-1ß) and tumor necrosis factor alpha (TNF-α) gene expression were also increased. By contrast, lysyl oxidase (LOX) expression and PPAR-γ protein levels were decreased in SHR as compared with normotensive animals. Only the high dose of eplerenone was able to reduce blood pressure and partially prevent LOX down-regulation in SHR. Both eplerenone doses significantly ameliorated interstitial fibrosis and tubular atrophy, reduced TGF-ß, CTGF and cytokine gene expression, and decreased Smad2 activation, while normalizing PPAR-γ protein levels. CONCLUSIONS: Mineralocorticoid receptor activation participates in hypertension-associated renal damage. This effect seems to involve stimulation of both fibrotic and inflammatory processes mediated (at least in part) by a down-regulation of PPAR-γ that can favour an up-regulation of the TGF-ß/Smad signalling pathway.

Los receptores β adrenérgicos en la enfermedad cardiovascular / The β Adrenergic Receptors in Cardiovascular Disease

La activación del sistema adrenérgico forma parte de un círculo vicioso que favorece la progresión de la insuficiencia cardiaca. Desde que se descubrieran los bloqueadores beta en los años 60, no han cesado los estudios centrados en descifrar el mecanismo de acción del sistema adrenérgico, y qué consecuencias tiene el bloqueo de los receptores adrenérgicos para mejorar los efectos deletéreos de la insuficiencia cardiaca. Actualmente se han descrito4 isoformas de los adrenérgicos. Los receptores más importantes en el sistema cardiovascular, debido a su densidad y a sus acciones fisiológicas, son los 1. Sin embargo, los receptores 2 y 3 adrenérgicos han tomado cierto protagonismo en las últimas décadas gracias a sus potenciales acciones cardioprotectoras. En esta revisión se quiere poner al día el sistema beta adrenérgico desde los aspectos moleculares más novedosos, polimorfismos que afectan a los receptores adrenérgicos, hasta el bloqueo de la señalización adrenérgica y las implicaciones clínicas que conlleva (AU)

Chronic adrenergic activation is part of a vicious cycle that leads to heart failure. Following the invention of blockers in the 60’s, there have been unending studies focused on deciphering the action mechanism of the adrenergic system and the consequences of the blockade of the adrenergic receptors in order to improve the harmful effects of the heart failure. Currently, 4 isoforms of the adrenoceptors have been described being the 1 the most important receptors in the cardiovascular system, due to their density and physiologicalactions. However, the 2 and 3 adrenergic receptors have taken on some importance in the last decades thanks to their potential cardio protective actions. This review will provide updated information on the beta adrenergic system going from the most novel molecular aspects, adrenergic receptors polymorphisms, up to the blockade of adrenergic signaling and the clinical implications involved (AU)

The plasma membrane calcium ATPase modulates calcium homeostasis, intracellular signaling events and function in platelets.

BACKGROUND: The plasma membrane calcium ATPase (PMCA) regulates localized signaling events in a variety of cell types, although its functional role in platelets remains undefined. OBJECTIVES: To investigate the role of PMCA in determining platelet intracellular calcium concentration ([Ca²(+) ](i) ) at rest and following agonist stimulation, and to define the corresponding effects upon different stages of platelet activation. METHODS: [Ca²(+) ](i) was continuously measured in Fura-2-loaded platelets and in vitro and in vivo functional analyses performed in the presence of the PMCA inhibitor carboxyeosin (CE). RESULTS: Concentrations of CE that selectively inhibited Ca²(+) extrusion through PMCA were established in human platelets. [Ca²(+) ](i) was elevated by CE in resting platelets, although collagen-stimulated Ca²(+) release was reduced. Impaired Ca²(+) mobilization upon agonist stimulation was accompanied by reduced dense granule secretion and impaired platelet aggregation. Platelet aggregation responses were also reduced in PMCA4(-/-) mice and in an in vivo mouse model of platelet thromboembolism. Conversely, inhibition of PMCA promoted the early and later stages of platelet activation, observed as enhanced adhesion to fibrinogen, and accelerated clot retraction. Investigations into the signaling mechanisms underlying CE-mediated inhibition of platelet aggregation implicated cGMP-independent vasodilator-stimulated phosphoprotein phosphorylation. CONCLUSIONS: Disruption of PMCA activity perturbs platelet Ca²(+) homeostasis and function in a time-dependent manner, demonstrating that PMCA differentially regulates Ca²(+) -dependent signaling events, and hence function, throughout the platelet activation process.

Platelet aggregation responses are critically regulated in vivo by endogenous nitric oxide but not by endothelial nitric oxide synthase.

BACKGROUND AND PURPOSE: Although exogenous nitric oxide (NO) clearly modifies platelet function, the role and the source of endogenous NO in vivo remain undefined. In addition, endothelial NO synthase (NOS-3) critically regulates vessel tone but its role in modulating platelet function is unclear. In this paper we have investigated the roles of endogenous NO and NOS-3 in regulating platelet function in vivo and determined the functional contribution made by platelet-derived NO. EXPERIMENTAL APPROACH: We used a mouse model for directly assessing platelet functional responses in situ in the presence of an intact vascular endothelium with supporting in vitro and molecular studies. KEY RESULTS: Acute NOS inhibition by N(omega)-nitro-L-arginine methyl ester hydrochloride (L-NAME) enhanced platelet aggregatory responses to thrombin and platelets were shown to be regulated primarily by NO sources external to the platelet. Elevation of endogenous NOS inhibitors to mimic effects reported in patients with cardiovascular diseases did not enhance platelet responses. Platelet responsiveness following agonist stimulation was not modified in male or female NOS-3(-/-) mice but responses in NOS-3(-/-) mice were enhanced by L-NAME. CONCLUSIONS AND IMPLICATIONS: Platelets are regulated by endogenous NO in vivo, primarily by NO originating from the environment external to the platelet with a negligible or undetectable role of platelet-derived NO. Raised levels of endogenous NOS inhibitors, as reported in a range of diseases were not, in isolation, sufficient to enhance platelet activity and NOS-3 is not essential for normal platelet function in vivo due to the presence of bioactive NO following deletion of NOS-3.

Papel de la aldosterona en las alteraciones vasculares funcionales y en el proceso inflamatorio asociados a la hipertensión en ratas / Role of aldosterone in vascular functional alterations and the inflammatory process associated to hypertension in rats

Objetivos: Estudiar la participación de la aldosterona en la disfunción vascular, el proceso inflamatorio y estrés oxidativo vascular asociado a hipertensión. Material y método: Se utilizaron ratas (n = 16) espontáneamente hipertensas (SHR) de 22 semanas de edad. La mitad de las ratas fueron tratadas durante 10 semanas con eplerenona a una dosis de 30 mg/kg/día (E-30). Se utilizaron ratas (n = 8) normotensas (WKY) como grupo de referencia. La presión arterial se midió de manera indirecta en la arteria caudal de la cola de las ratas. Al final del tratamiento las ratas se sacrificaron y se pesaron los corazones. Se evaluó la función endotelial en anillos aórticos en respuesta a la acetilcolina. La expresión del ARN mensajero (ARNm) de las interleucinas 1 β y 6 (IL-1β e IL-6), del factor de necrosis tumoral α (TNF-α), de la enzima óxido nítrico endotelial (eNOS) y de la subunidad p22phox de la enzima NAD(P)H oxidasa se midió en la aorta de las ratas. Resultados: Las SHR presentaron unos valores de presión arterial sistólica mayores (p < 0,05) que las ratas controles WKY (199,8±4,2 frente a 125,3±2,0 mmHg). El tratamiento con eplerenona redujo (p < 0,05) ligeramente las cifras de presión arterial en las ratas hipertensas (E30; 181,0±2,0 mmHg). No hubo diferencias en el peso corporal de las ratas, sin embargo el peso relativo del corazón de las ratas hipertensas era significativamente mayor respecto a las ratas normotensas y se normalizó con el tratamiento con eplerenona. La relajación a acetilcolina estaba significativamente reducida en las ratas SHR así como la expresión vascular de la eNOS. Sin embargo, las ratas hipertensas presentaron una sobreexpresión vascular del ARNm de IL-1β, IL-6, TNF-α y p22phox respecto a las WKY (p < 0,05). El tratamiento con eplerenona normalizó la función endotelial en las ratas hipertensas; aumento la expresión del ARNm de eNOS y redujo la expresión vascular de las citocinas IL-1β, IL-6, TNF-α, así como de la p22phox. Conclusiones: La aldosterona participa en las alteraciones funcionales vasculares en las SHR reduciendo la biodisponibilidad de óxido nítrico, aumentando el estrés oxidativo y el proceso inflamatorio vascular(AU)

Objetives: To study the participation of aldosterone in the vascular dysfunction, inflammatory process and vascular oxidative stress associated to hypertension. Material and methods: Half of the group of 22 week-old spontaneously hypertensive rats (n=16) were treated with eplerenone (E-30; 30 mg/kg/day) for 10 weeks. Normotensive rats (WKY; n = 8) were used as reference group. Systolic arterial pressure (SAP) was measured by the tail-cuff method. Body weight and heart weight were measured at the end of the treatment. Endothelium-dependent relaxations, as well as vascular mRNA expression of interleukin 1 β and 6 (IL-1β and IL-6), tumor necrosis factor alpha (TNF-α), of endothelial nitric oxide synthase (eNOS), NAD(P)H oxidase subunit p22phox were studied in aorta from SHR untreated or treated with eplerenone. Results: SHR showed higher levels of systolic blood pressure (p < 0.05) as compare with control rats (199.8±4.2 vs. 125.33±2.0 mmHg). Although there were no differences in the body weight among the groups, hypertensive rats had a higher relative heart weight compare to normotensive rats and it was normalize with the treatment of eplerenone (p < 0.05). SHR showed higher vascular mRNA expression of IL-1β, IL-6, TNF-α and p22phox compared to WKY (p < 0.05). Treatment with eplerenone slightly reduced (p < 0.05) blood pressure in hypertensive rats (E30; 181.0±2.0 mmHg) and normalized acetylcholine relaxations. Eplerenone enhanced (p < 0.05) eNOS and reduced p22phox, IL-1β, IL-6, TNF-α of aortic mRNA expressions in SHR. Conclusions: In SHR, aldosterone participates in the functional vascular alterations through the diminution of nitric oxide availability and the enhancement of the inflammatory process and the increase of vascular oxidative stress(AU)

Inflamación, disfunción endotelial e hipertensión arterial / Inflammation, endothelial dysfunction and hypertension

El proceso inflamatorio agudo y crónico determinan cambios importantes en los componentes de la sangre, tanto celulares como los no celulares, incluidos proteínas, lípidos, hormonas, citocinas, así como otras moléculas. Algunos de estos marcadores de inflamación como las citocinas, y especialmente la proteína C reactiva (PCR), se consideran en la actualidad predictores de eventos cardiovasculares. Además, la PCR favorece el desarrollo de la disfunción endotelial al reducir la producción de óxido nítrico (NO), sugiriendo, por tanto, un papel de la inflamación en el desarrollo de las alteraciones de la función endotelial.Asimismo existen datos que indican que la disfunción endotelial favorece el desarrollo inflamatorio.Una relación compleja también se ha observado entre inflamación e hipertensión arterial; niveles elevados de presión arterial se asocian con un incremento de los niveles plasmáticos de algunos marcadores de inflamación y, a su vez, una elevación de los marcadores de inflamación parecen predecir el riesgo de desarrollar hipertensión (AU)

Hipercolesterolemia y disfunción endotelial: mecanismos implicados / Hypercholesterolemia and endothelial dysfunction: mechanisms involved

El endotelio desempeña un papel clave en la regulación de la función vascular al liberar, en respuesta a distintos estímulos, numerosos factores vasoactivos. La hiperlipidemia, así como otros factores de riesgo cardiovascular, alteran ese papel homeostático que desempeña el endotelio en la regulación de la función vascular. Uno de los mecanismos fundamentales que subyacen a la disfunción endotelial parece ser una disminución en la disponibilidad de óxido nítrico (NO), lo que permite la sobreexpresión de las acciones de factores que se oponen a los efectos beneficiosos y protectores de éste sobre la pared vascular. Diversos mecanismos podrían ser responsables de esta menor disponibilidad de NO, desde alteraciones en su síntesis a una mayor degradación como consecuencia de un aumento del estrés oxidativo. En pacientes hipercolesterolémicos la reducción de los niveles de colesterol conlleva una mejoría de la función endotelial, lo que indicaría que la elevación de dichos niveles podría activar diversos mecanismos que alteraran el normal funcionamiento del endotelio. Sin embargo, existen otros grupos de fármacos, como los antioxidantes o los que bloquean el sistema renina-angiotensina, que han demostrado un efecto beneficioso sobre la función endotelial tanto en estudios clínicos como experimentales (AU)

Alteraciones del endotelio en la hipertensión / Endothelial dysfunction in hypertension

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Papel de la agiotensina II en el desarrollo aterosclerótico: efecto de su bloqueo / Role of angiotensin II in the development of atherosclerosis: effect of blockade

La angiotensina II, el principal efector del sistema renina-angiotensina, ejerce un papel importante en la génesis y en las complicaciones de la aterosclerosis. La angiotensina II estimula la producción de especies reactivas de oxígeno en el vaso que desempeñan un papel clave en la disfunción endotelial y en la oxidación de las lipoproteínas de baja densidad (LDL). Asimismo, este péptido participa en la inducción de la respuesta inflamatoria en la pared vascular mediante la producción de moléculas de adhesión y citoquinas quimiotácticas y proinflamatorias. La angiotensina II, además, estimula la proliferación y migración de células de músculo liso y modula el cambio fenotípico de las mismas dando lugar a un aumento de la síntesis de la matriz extracelular. Finalmente, la angiotensina II también participa en las complicaciones de la aterosclerosis al favorecer la ruptura de la placa y trombogenicidad de la misma. En consecuencia, el sistema renina-angiotensina desempeña un papel clave en la patofisiología de la aterosclerosis, por lo que su bloqueo ejercerá un efecto beneficioso sobre el desarrollo aterosclerótico previniendo las alteraciones trombóticas asociadas a él (AU)

Atorvastatin prevents glomerulosclerosis and renal endothelial dysfunction in hypercholesterolaemic rabbits.

BACKGROUND: Numerous studies have shown that elevated plasma cholesterol can exacerbate renal disease. However, the effect of lipids on renal structure and vascular function in normal kidneys is less well established. Therefore, the aim of this study was to evaluate the impact of hypercholesterolaemia on glomerular structure and vascular reactivity of segmental arteries in rabbits. In addition, we also studied whether or not atorvastatin can prevent these structural and vascular alterations in hypercholesterolaemic rabbits. METHODS: Male New Zealand rabbits were fed either a normal rabbit chow or a diet containing 1% cholesterol and treated or not with atorvastatin (1 mg/kg/day) for 12 weeks. Dose-response curves to acetylcholine (10(-9)-10(-4) mol/l) and sodium nitroprusside (10(-9)-10(-4) mol/l) were studied in segmental arteries in the presence or absence of the thromboxane A2/PGH2 receptor antagonist ifetroban (10(-5) mol/l). Glomerular size and structure were also evaluated. RESULTS: Compared with control animals, hypercholesterolaemic rabbits presented glomerular hypertrophy and several types of injuries (capillary collapse, hyalinosis and alterations of Bowman's capsule), suggesting diffuse glomerulosclerosis. Segmental arteries also showed relaxing responses to acetylcholine and sodium nitroprusside which were lower than and similar to, respectively, those of control animals. The presence of ifetroban improved the acetylcholine response only in hypercholesterolaemic rabbits. Atorvastatin treatment prevented vascular and most glomerular changes associated with hypercholesterolaemia even in the presence of very high cholesterol levels. CONCLUSIONS: Atorvastatin exerts a protective effect on renal damage associated with hypercholesterolaemia even in the presence of deleterious levels of plasma cholesterol.

Relevance of endothelium-derived hyperpolarizing factor in the effects of hypertension on rat coronary relaxations.

OBJECTIVES: To evaluate the relative participation of nitric oxide (NO), endothelium-derived hyperpolarizing factor (EDHF) and prostanoids in the relaxing responses induced by acetylcholine and isoproterenol in isolated coronary arteries from adult Wistar- Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). DESIGN AND METHODS: Male adult WKY rats and SHR were used in the study. Segments from left coronary arteries (approximately 350-380 microm internal diameter and 2 mm long) were mounted in an isometric myograph and pre-contracted with serotonin. Dose-response curves to acetylcholine and isoproterenol were carried out in absence and presence of the NO synthesis inhibitor NG-nitro-L-arginine methyl ester (LNAME), the inhibitor of the cyclo-oxygenase, indomethacin and KCI. Areas under the respective dose-response curves were used to calculate the approximate relative participation of NO, EDHF and prostanoids. RESULTS: Relaxations to either acetylcholine or isoproterenol were lower in SHR than in WKY rats. In WKY rats, presence of LNAME diminished (P< 0.05) relaxation to acetylcholine from 10(-9) to 10(-6) mol/l, and induced a contracting response at 10(-5) and 10(-4) mol/l of acetylcholine. Addition of indomethacin did not significantly affect dose-related relaxation to acetylcholine 10(-9) to 10(-6) mol/l in WKY rats, and reduced (P < 0.05) the contracting response observed at 10(-5) mol/l of acetylcholine. In SHR, addition of LNAME markedly reduced (P< 0.05) acetylcholine relaxations, but did not produce any contracting effect. Addition of indomethacin on top of LNAME slightly (P< 0.05) enhanced relaxing response to acetylcholine in SHR. Presence of LNAME in the media diminished (P < 0.05) relaxation to isoproterenol in both WKY rats and SHR. Addition of indomethacin on top of LNAME increased (P< 0.05) isoproterenol-relaxing response to levels similar to and higher than control conditions in WKY rats and SHR, respectively. Addition of KCI blunted both acetylcholine- and isoproterenol-relaxations in both groups. CONCLUSIONS: NO and EDHF are the main endothelium-derived relaxing factors underlying acetylcholine and isoproterenol relaxations in rat coronary arteries, respectively. EDHF reduction, and not only NO reduction play a key role in the diminished coronary relaxations induced by acetylcholine and isoproterenol in SHR. An arachidonic acid derivative with contracting activity released by acetylcholine and isoproterenol in a differential manner, could oppose the relaxing actions of NO and EDHF.