Chronic nitric oxide synthase inhibition by NW -nitro- L-arginine methyl ester (L-NAME) associated with salt overload (HS) is a model of chronic kidney disease (CKD), originally described in our laboratory. This model has been used widely to understand the mechanisms that are involved in the progression of CKD, currently a major public health problem. In our initial description and in subsequent studies, we showed that this model is characterized by severe glomerular and systemic hypertension, proteinuria, and interstitial fibrosis, glomerulosclerosis and glomerular ischemia. These abnormalities are associated with an inflammatory process that affects the glomeruli and, especially, the interstitial compartment. We and others demonstrated that treatment with MMF, an immunosuppressant that inhibits lymphocyte proliferation, attenuates inflammation and renal damage in this model.The mechanisms of inflammation and renal injury in the L-NAME+HS model are poorly understood. It is possible that at least part of this process is due to activation of innate immunity, as demonstrated in other clinical and experimental instances of CKD. The limited data available suggest that the NF-kB system, which integrates one of the innate immunity signaling pathways (called Signal 1), may be activated after inhibition of NO synthesis. No evidence is available as to other pathways of innate immunity, such as the NLRP3 inflammasome cascade (called Signal 2).The aim of this study is to verify the involvement of the NF-kB system and the NLRP3 inflammasome in the development of hypertension and renal injury in the model of chronic inhibition of nitric oxide associated with salt overload.
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(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
FREGNAN ZAMBOM, FERNANDA FLORENCIA;
OLIVEIRA, KARIN CARNEIRO;
FAUSTINO, VIVIANE DIAS;
AVILA, VICTOR FERREIRA;
ALBINO, AMANDA HELEN;
ALARCON ARIAS, SIMONE COSTA;
VOLPINI, RILDO APARECIDO;
AVANCINI COSTA MALHEIROS, DENISE MARIA;
SARAIVA CAMARA, NIELS OLSEN;
FUJIHARA, CLARKE KAZUE.
Pathogenic role of innate immunity in a model of chronic NO inhibition associated with salt overload.
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY,
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