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Role of renal sympathetic nerves on cardiovascular and renal alterations in renovascular hypertension

Grant number: 13/22522-9
Support type:Regular Research Grants
Duration: September 01, 2014 - August 31, 2017
Field of knowledge:Biological Sciences - Physiology
Principal Investigator:Ruy Ribeiro de Campos Junior
Grantee:Ruy Ribeiro de Campos Junior
Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
Assoc. researchers:Adriana Castello Costa Girardi ; Alex Yuri Simões Sato ; Cassia Marta de Toledo Bergamaschi ; Guiomar Nascimento Gomes

Abstract

The renovascular hypertension dependent of angiotensin II (Ang II) is characterized by sympathetic overactivity and, therefore, has a strong neurogenic component. Previous studies from our laboratory showed that in the 2 kidney-one clip model (2K-1C) in rats the increased renal sympathetic nerve activity (RSNA) contributes for the development of hypertension and there is an increase in the expression of AT1 Ang II receptor in brain regions involved with the cardiovascular control as well as in the ischemic kidney. Such data suggest that there is an interaction between central and renal mechanisms related to the Ang II actions leading to Sympathoexcitation in renovascular hypertension. Thus, our hypothesis is that the sympathetic overactivity in renovascular hypertension leads to changes in the AT1 and AT2 Ang II receptors expression in a differential way in the ischemic and contralateral kidney of 2K-1C rats, leading therefore, morphological and physiological renal changes leading to increase in blood pressure. The major aim of the present project will evaluate the effects of renal denervation of ischemic kidney, that releases renin, from hypertensive rats leads to changes in the expression of Ang II receptors (AT1 and AT2) in the cortex and medulla of ischemic and contralateral kidney. Furthermore, considering that this is a model with a strong neurogenic component, the expression of such receptors will be evaluated in the regions of central nervous system related to cardiovascular regulation, such as, RVLM and PVN, that are involved in the control of sympathetic vasomotor activity and RSNA. For comparison, in another series of experiments the rats will be treated with Losartan, an AT1 receptor antagonist (30 mg/Kg/day), or a non-specific antihypertensive drug, hidralazyn (25 mg/Kg/day), to differentiate the changes related to fall in blood pressure and reduction in RSNA. The data, altogether will improve our understanding of the cross-talk between the central nervous system and the kidneys regarding the hypertension. (AU)

Scientific publications (10)
(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)
NISHI, ERIKA E.; ALMEIDA, VITOR R.; AMARAL, FERNANDA G.; SIMON, KARIN A.; FUTURO-NETO, HENRIQUE A.; PONTES, ROBERTO B.; CESPEDES, JULIANA G.; CAMPOS, RUY R.; BERGAMASCHI, CASSIA T. Melatonin attenuates renal sympathetic overactivity and reactive oxygen species in the brain in neurogenic hypertension. HYPERTENSION RESEARCH, v. 42, n. 11, p. 1683-1691, NOV 2019. Web of Science Citations: 1.
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 JUL 2019. Web of Science Citations: 0.
NISHI, ERIKA E.; LOPES, NATHALIA R.; GOMES, GUIOMAR N.; PERRY, JULIANA C.; SATO, ALEX Y. S.; NAFFAH-MAZZACORATTI, MARIA G.; BERGAMASCHI, CASSIA T.; CAMPOS, RUY R. Renal denervation reduces sympathetic overactivation, brain oxidative stress, and renal injury in rats with renovascular hypertension independent of its effects on reducing blood pressure. HYPERTENSION RESEARCH, v. 42, n. 5, p. 628-640, MAY 2019. Web of Science Citations: 5.
NISHI, ERIKA E.; MARTINS, BEATRIZ S.; MILANEZ, MAYCON I. O.; LOPES, NATHALIA R.; DE MELO, JR., JOSE F.; PONTES, ROBERTO B.; GIRARDI, ADRIANA C.; CAMPOS, RUY R.; BERGAMASCHI, CASSIA T. Stimulation of renal afferent fibers leads to activation of catecholaminergic and non-catecholaminergic neurons in the medulla oblongata. AUTONOMIC NEUROSCIENCE-BASIC & CLINICAL, v. 204, p. 48-56, MAY 2017. Web of Science Citations: 2.
VEIGA, GLAUCIA L.; NISHI, ERIKA E.; ESTRELA, HEDER F.; LINCEVICIUS, GISELE S.; GOMES, GUIOMAR N.; SIMOES SATO, ALEX Y.; CAMPOS, RUY R.; BERGAMASCHI, CASSIA T. Total renal denervation reduces sympathoexcitation to different target organs in a model of chronic kidney disease. AUTONOMIC NEUROSCIENCE-BASIC & CLINICAL, v. 204, p. 81-87, MAY 2017. Web of Science Citations: 5.
GARCIA, MICHELLE L.; PONTES, ROBERTO B.; NISHI, ERIKA E.; IBUKI, FLAVIA K.; OLIVEIRA, VANESSA; SAWAYA, ALEXANDRA C. H.; CARVALHO, PATRICIA O.; NOGUEIRA, FERNANDO N.; FRANCO, MARIA DO CARMO; CAMPOS, RUY R.; OYAMA, LILA M.; BERGAMASCHI, CASSIA T. The antioxidant effects of green tea reduces blood pressure and sympathoexcitation in an experimental model of hypertension. Journal of Hypertension, v. 35, n. 2, p. 348-354, FEB 2017. Web of Science Citations: 15.
SHIMOURA, CAROLINE G.; LINCEVICIUS, GISELE S.; NISHI, ERIKA E.; GIRARDI, ADRIANA C. C.; SIMON, KARIN A.; BERGAMASCHI, CASSIA T.; CAMPOS, RUY R. Increased Dietary Salt Changes Baroreceptor Sensitivity and Intrarenal Renin-Angiotensin System in Goldblatt Hypertension. AMERICAN JOURNAL OF HYPERTENSION, v. 30, n. 1, p. 28-36, JAN 2017. Web of Science Citations: 3.
ESTRELA, HEDER F. G.; DAMASIO, ELAINE S.; FONSECA, EDUARDO K. U. N.; BERGAMASCHI, CASSIA T.; CAMPOS, RUY R. Differential Sympathetic Vasomotor Activation Induced by Liver Cirrhosis in Rats. PLoS One, v. 11, n. 4 APR 7 2016. Web of Science Citations: 1.
LINCEVICIUS, GISELE S.; SHIMOURA, CAROLINE G.; NISHI, ERIKA E.; PERRY, JULIANA C.; CASARINI, DULCE E.; GOMES, GUIOMAR N.; BERGAMASCHI, CASSIA T.; CAMPOS, RUY R. Aldosterone Contributes to Sympathoexcitation in Renovascular Hypertension. AMERICAN JOURNAL OF HYPERTENSION, v. 28, n. 9, p. 1083-1090, SEP 2015. Web of Science Citations: 15.
PONTES, ROBERTO B.; CRAJOINAS, RENATO O.; NISHI, ERIKA E.; OLIVEIRA-SALES, ELIZABETH B.; GIRARDI, ADRIANA C.; CAMPOS, RUY R.; BERGAMASCHI, CASSIA T. Renal nerve stimulation leads to the activation of the Na+/H+ exchanger isoform 3 via angiotensin II type I receptor. AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY, v. 308, n. 8, p. F848-F856, APR 15 2015. Web of Science Citations: 20.

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