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1.
Diabetes ; 59(10): 2597-602, 2010 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-20622163

RESUMEN

OBJECTIVE: To evaluate modifications of arterial structure, gene expression, and function in our model of rats exposed to maternal diabetes. RESEARCH DESIGN AND METHODS: Morphometric analyses of elastic vessels structure and determination of thoracic aortic gene expression profile with oligonucleotide chips (Agilent, G4130, 22k) were performed before the onset of established hypertension (3 months). RESULTS: Arterial parameters of in situ fixed thoracic aorta were not significantly different between control mother offspring and diabetic mother offspring (DMO). The aortic gene expression profile of DMO is characterized by modifications of several members of the arachidonic acid metabolism including a twofold underexpression of prostacyclin receptor, which could contribute to decreased vasodilatation. This was confirmed by ex vivo experiments on isolated aortic rings. Pharmacological studies on conscious rats showed that systolic blood pressure decline in response to a PGI(2) analog was impaired in DMO rats. CONCLUSIONS: These results suggest an abnormal vascular fetal programming of prostacyclin receptor in rats exposed in utero to maternal hyperglycemia that is associated with impaired vasodilatation and may be involved in the pathophysiology of hypertension in this model.


Asunto(s)
Diabetes Mellitus Experimental/fisiopatología , Complicaciones del Embarazo/fisiopatología , Receptores de Epoprostenol/genética , Animales , Aorta Torácica/embriología , Aorta Torácica/fisiología , Ácido Araquidónico/metabolismo , Presión Sanguínea , ADN Complementario/genética , Diabetes Mellitus Experimental/genética , Femenino , Perfilación de la Expresión Génica , Regulación del Desarrollo de la Expresión Génica , Análisis de Secuencia por Matrices de Oligonucleótidos , Embarazo , Complicaciones del Embarazo/genética , ARN/genética , ARN/aislamiento & purificación , Ratas , Ratas Sprague-Dawley , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Vasodilatación
2.
Am J Physiol Lung Cell Mol Physiol ; 292(6): L1422-31, 2007 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-17322280

RESUMEN

Pseudomonas aeruginosa is a gram-negative bacilli frequently encountered in human pathology. This pathogen is involved in a large number of nosocomial infections and chronic diseases. Herein we investigated the effects of polyunsaturated fatty acids (PUFA) in chronic Pseudomonas aeruginosa lung infection. C57BL/6 mice were fed for 5 wk with specifically designed diets with high contents in either omega-3 (omega-3) or omega-6 PUFA and compared to a control diet. P. aeruginosa included in agarose beads was then instilled intratracheally, and the animals were studied for 7 days. On the 4th day, the mice fed with the omega-3 diet had a higher lean body mass gain and a lower omega-6:omega-3 ratio of fatty acids extracted from the lung tissue compared with the other groups (P < 0.05). The omega-3 group had the lowest mortality. Distal alveolar fluid clearance (DAFC) as well as the inflammatory response and the cellular recruitment were higher in the omega-3 group on the 4th day. The effect on DAFC was independent of alpha-epithelial Na(+) channels (alpha-ENaC), beta-ENaC, and alpha(1)-Na-K-ATPase mRNA expressions, which were not altered by the different diets. In conclusion, a diet enriched in omega-3 PUFA can change lung membrane composition and improve survival in chronic pneumonia. This effect on survival is probably multifactorial involving the increased DAFC capacity as well as the optimization of the initial inflammatory response. This work suggests that a better control of the omega-6/omega-3 PUFA balance may represent an interesting target in the prevention and/or control of P. aeruginosa infection in patients.


Asunto(s)
Ácidos Grasos Omega-3/farmacología , Neumonía Bacteriana/tratamiento farmacológico , Infecciones por Pseudomonas/tratamiento farmacológico , Pseudomonas aeruginosa , Alimentación Animal , Animales , Líquido del Lavado Bronquioalveolar/inmunología , Canales Epiteliales de Sodio/genética , Agua Pulmonar Extravascular/metabolismo , Interleucina-6/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Neutrófilos/inmunología , Neumonía Bacteriana/inmunología , Infecciones por Pseudomonas/inmunología , Alveolos Pulmonares/metabolismo , Alveolos Pulmonares/microbiología , ARN Mensajero/metabolismo , ATPasa Intercambiadora de Sodio-Potasio/genética , Factor de Necrosis Tumoral alfa/metabolismo , Pérdida de Peso
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