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Functional and molecular actions of renal nerve in experimental chronic renal failure


The prevalence of chronic kidney disease (CKD) is increasing worldwide and the main contributors to CKD progression are arterial hypertension (AH) and diabetes. Despite advances in pharmacological treatments with antihypertensive and anti-diabetic drugs, the alarming number of patients with nephropathy shows the need for new therapeutic strategies. The sympathetic nervous system (SNS) has been highlighted as an important therapeutic target for AH through renal denervation in patients and experimental models. Clinical and experimental studies have shown that the denervation procedure, which removes both the renal sympathetic and sensory fibers, promotes not only renoprotective effects, but also improves cardiac and vascular function, glucose metabolism and insulin sensitivity. In CKD, several mechanisms lead to cardiac and renal dysfunction, such as the renin-angiotensin system (RAS), aldosterone, endothelin, inflammation, oxidative stress and fibrosis. The hypothesis of the present project is that the renal nerves play an important role in determining the cardiovascular and renal alterations in CKD. CKD will be induced by the experimental 5/6 nephrectomy model in Wistar rats. Total renal denervation, selective denervation of the renal afferent fibers and/or renin-angiotensin system blockade will be performed after 5 weeks of CKD induction, and 3 weeks later the following parameters will be evaluated: blood pressure, heart rate, sympathetic nerve activity to different beds, cardiac and renal function and fibrosis, systemic and renal oxidative stress and inflammation. In addition, tubular or glomerular proteinuria, NADPH oxidase subunits and Rho kinase activity marker, pMYPT1, will be evaluated by western blotting and serum copeptin and urinary angiotensinogen will be quantified by ELISA. Data obtained from the present project will contribute to the understanding of underlying mechanisms in AH and thereby contribute to the development and improvement of new therapeutic strategies to treat CKD. These studies will contribute to the understanding of mechanisms associated with the antihypertensive effect of renal denervation in humans and animal models. (AU)

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Scientific publications (11)
(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)
MILANEZ, MAYCON I. O.; MARTINS, GUSTAVO R.; NISHI, ERIKA E.; BERGAMASCHI, CASSIA T.; CAMPOS, RUY R.. Differential sympathetic vasomotor control by spinal AT(1) and V1 a receptors in the acute phase of hemorrhagic shock. European Journal of Pharmacology, v. 866, . (18/02671-3, 18/01898-4)
VEIGA, AMANDA C.; MILANEZ, MAYCON I. O.; CAMPOS, RUY R.; BERGAMASCHI, CASSIA T.; NISHI, ERIKA E.. The involvement of renal afferents in the maintenance of cardiorenal diseases. AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY, v. 320, n. 1, p. R88-R93, . (18/01898-4, 18/02671-3, 18/11909-3, 17/03905-5)
GARCIA, MICHELLE L.; MILANEZ, MAYCON I. O.; NISHI, ERIKA E.; SATO, ALEX Y. S.; CARVALHO, POLLIANE M.; NOGUEIRA, FERNANDO N.; CAMPOS, RUY R.; OYAMA, LILA M.; BERGAMASCHI, CASSIA T.. Retroperitoneal adipose tissue denervation improves cardiometabolic and autonomic dysfunction in a high fat diet model. Life Sciences, v. 283, . (18/02671-3)
MILANEZ, M. I. O.; LIBERATORE, A. M. A.; NISHI, E. E.; BERGAMASCHI, C. T.; CAMPOS, R. R.; KOH, I. H. J.. atterns of renal and splanchnic sympathetic vasomotor activity in an animal model of survival to experimental sepsi. Brazilian Journal of Medical and Biological Research, v. 55, n. 1, . (17/21052-0, 18/02671-3, 18/01898-4)
VEIGA, AMANDA C.; MILANEZ, MAYCON I. O.; FERREIRA, GIOVANNA R.; LOPES, NATHALIA R.; SANTOS, CAMILA P.; DE ANGELIS, KATIA; GARCIA, MICHELLE L.; OYAMA, LILA M.; GOMES, GUIOMAR N.; NOGUEIRA, FERNANDO N.; et al. Selective afferent renal denervation mitigates renal and splanchnic sympathetic nerve overactivity and renal function in chronic kidney disease-induced hypertension. Journal of Hypertension, v. 38, n. 4, p. 765-773, . (18/02671-3, 13/23741-6, 17/03905-5)
MILANEZ, MAYCON I. O.; NISHI, ERIKA E.; MENDES, RODRIGO; ROCHA, ANTONIO A.; BERGAMASCHI, CASSIA T.; CAMPOS, RUY R.. Renal sympathetic activation triggered by the rostral ventrolateral medulla is dependent of spinal cord AT1 receptors in Goldblatt hypertensive rats. Peptides, v. 146, . (18/01898-4, 18/02671-3, 19/25295-0)
LOPES, NATHALIA R.; MILANEZ, MAYCON I. O.; MARTINS, BEATRIZ S.; VEIGA, AMANDA C.; FERREIRA, GIOVANNA R.; GOMES, GUIOMAR N.; GIRARDI, ADRIANA C.; CARVALHO, POLLIANE M.; NOGUEIRA, FERNANDO N.; CAMPOS, RUY R.; et al. Afferent innervation of the ischemic kidney contributes to renal dysfunction in renovascular hypertensive rats. PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, v. 472, n. 3, . (17/12383-2, 15/23858-6, 18/02671-3, 16/22140-7)
MILANEZ, MAYCON I. O.; VEIGA, AMANDA C.; MARTINS, BEATRIZ S.; PONTES, ROBERTO B.; BERGAMASCHI, CASSIA T.; CAMPOS, RUY R.; NISHI, ERIKA E.. Renal Sensory Activity Regulates the gamma-Aminobutyric Acidergic Inputs to the Paraventricular Nucleus of the Hypothalamus in Goldblatt Hypertension. FRONTIERS IN PHYSIOLOGY, v. 11, . (17/03905-5, 20/02617-9, 18/02671-3, 18/01898-4, 18/11909-3, 15/23809-5)
MILANEZ, MAYCON I. O.; SILVA, ADILSON M.; PERRY, JULIANA C.; FABER, JEAN; NISHI, ERIKA E.; BERGAMASCHI, CASSIA T.; CAMPOS, RUY R.. Pattern of sympathetic vasomotor activity induced by GABAergic inhibition in the brain and spinal cord. PHARMACOLOGICAL REPORTS, v. 72, n. 1, p. 67-79, . (18/01898-4, 18/02671-3)
ZAMBRANO, I, LYSIEN; PONTES, ROBERTO B.; GARCIA, MICHELLE L.; NISHI, ERIKA E.; NOGUEIRA, FERNANDO N.; HIGA, ELISA M. S.; CESPEDES, JULIANA G.; BERGAMASCHI, CASSIA T.; CAMPOS, RUY R.. Pattern of sympathetic vasomotor activity in a model of hypertension induced by nitric oxide synthase blockade. PHYSIOLOGICAL REPORTS, v. 7, n. 14, . (18/02671-3, 13/22522-9, 13/23741-6)
MILANEZ, MAYCON I. O.; NISHI, ERIKA E.; ROCHA, ANTONIO A.; BERGAMASCHI, CASSIA T.; CAMPOS, RUY R.. Interaction between angiotensin II and GABA in the spinal cord regulates sympathetic vasomotor activity in Goldblatt hypertension. Neuroscience Letters, v. 728, . (18/02671-3, 18/01898-4)

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