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The role of sleep and sildenafil in the progression of chronic kidney disease: a new therapeutic approach

Grant number: 12/21794-2
Support Opportunities:Regular Research Grants
Duration: February 01, 2013 - January 31, 2015
Field of knowledge:Biological Sciences - Physiology - General Physiology
Principal Investigator:Monica Levy Andersen
Grantee:Monica Levy Andersen
Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
Associated researchers:Sergio Tufik

Abstract

Chronic kidney disease (CKD) is a disease with high morbidity and mortality, whose incidence and prevalence have increased in epidemic proportions in Brazil and worldwide. Patients with CKD on dialysis are driven to live every day with an incurable disease that requires a long painful treatment with high-impact changes in their quality of life. Along with the evolution of the disease and its complications, there is the development of sexual dysfunction and hypertension, comorbidities highly prevalent and associated with oxidative stress and reduced availability of nitric oxide (NO). Due to the constant exposure to stressful situations, sleep restriction is another risk factor inherent to the lifestyle of CKD patients. It is known, however, that sleep plays essential role in the restoration and maintenance of body homeostasis, which could means hypothetically that chronic conditions of sleep deprivation in CKD may worsen the disease evolution. Therefore, this study aims to investigate the effects of a chronic treatment with low doses of sildenafil, whose mechanism of action involves the stimulation of NO pathway in view of possible negative effects enhanced by sleep restriction on blood pressure, kidney function and reproductive behavior of an animal model of CKD. For this, adult male rats will be used initially distributed into 4 groups: control group treated with vehicle or sildenafil, and nephrectomized group treated with vehicle or sildenafil, which will be subdistributed after 46 days into: sleep restricted or home-cage. At the end, sexual behavior, blood pressure and heart rate, biochemical and inflammatory profile, as well as sexual and stress hormones will be evaluated. Possible underlying molecular mechanisms will be investigated by gene expression of oxidative stress and NO pathways. Morphologic evaluation will be done in kidney and testis tissues. (AU)

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Scientific publications
(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)
ALBUQUERQUE, RACHEL GIMENES; OKAZAKI, KEITY MEY; HIROTSU, CAMILA; TOMIMORI, JANE; TUFIK, SERGIO; ANDERSEN, MONICA LEVY. Sleep, Hansen's disease and the immune system - A not so harmonic triad. Medical Hypotheses, v. 84, n. 5, p. 456-459, . (14/00923-4, 12/21794-2, 14/15259-2)
ALBUQUERQUE, RACHEL GIMENES; DIAS DA ROCHA, MARCO ALEXANDRE; HIROTSU, CAMILA; HACHUL, HELENA; BAGATIN, EDILEIA; TUFIK, SERGIO; ANDERSEN, MONICA LEVY. A randomized comparative trial of a combined oral contraceptive and azelaic acid to assess their effect on sleep quality in adult female acne patients. ARCHIVES OF DERMATOLOGICAL RESEARCH, v. 307, n. 10, p. 905-915, . (12/21794-2, 14/15259-2, 14/00923-4)
HIROTSU, CAMILA; NOGUEIRA, HELOISA; ALBUQUERQUE, RACHEL G.; TOMIMORI, JANE; TUFIK, SERGIO; ANDERSEN, MONICA L.. The bidirectional interactions between psoriasis and obstructive sleep apnea. INTERNATIONAL JOURNAL OF DERMATOLOGY, v. 54, n. 12, p. 1352-1358, . (12/21794-2, 14/15259-2, 14/00923-4)

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