Cardiovascular autonomic control in toll-like receptor 9 knockout mice with hypertension induced by angiotensin II.

• Grant number: 15/21976-1
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: March 01, 2016
• End date: January 29, 2019
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Helio Cesar Salgado
• Grantee: Fernanda Luciano Rodrigues
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 13/20549-7 - New insights in cardiovascular regulation under physiological and pathophysiological condition, AP.TEM

Abstract

The autonomic nervous system modulates the immune system and the sympathetic overactivity and/or decreased parasympathetic activity leads to inflammatory processes that affect the body as a whole, including the cardiovascular system. The immune system is involved in several cardiovascular diseases, including hypertension. The innate immune system is the major activator of the adaptive immune response and toll like receptors (TLR) are important components of this system, recognizing pathogen-associated molecular patterns (PAMP), as well as endogenous molecular structures released by cell death and tissue damage, known as DAMP (damage-associated molecular patterns). At least 11 TLR subtypes have been described. The TLR are expressed on a variety of immune cells as well as in non-immune cells including, for example, the endothelium. Several studies have demonstrated the involvement of TLR, especially TLR2 and TLR4, in the cardiovascular autonomic control, as well as in the genesis and progression of cardiovascular diseases. The involvement of TLR in the hypertension has been shown in different experimental models and there is evidence of their participation in the neural control of blood pressure (BP). Studies have demonstrated that TLR9 is involved in pre-eclampsia, as well as their activation seems to contribute to the increase in BP in spontaneously hypertensive rats (SHR). Recently, we demonstrated that TLR9 negatively modulate the parasympathetic nervous system. Thus, we hypothesized that TLR9 may play an important role in the hypertension induced by angiotensin II (Ang II) infusion, leading to inflammation and contributing to the increase in BP. Thus, TLR9 knockout (TLR9 KO) mice would be protected, at least in part, from the deleterious effects of Ang II infusion. In this study, we will evaluate the cardiac function, the baroreflex, the cardiac autonomic tone, as well as the BP and pulse interval (PI) variability in TLR9 KO mice, subjected, or not, to the hypertension induced by Ang II infusion. Possible mechanisms by which TLR9 contribute to the cardiovascular changes in this model will be also evaluated.

Scientific publications

(4)

(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)

RODRIGUES, FERNANDA LUCIANO; FAIS, RAFAEL S.; PEREIRA, MARLIA G. A. G.; GARCIA-CAIRASCO, NORBERTO; TOSTES, RITA C.; CARNEIRO, FERNANDO S.. Erectile Dysfunction in Wistar Audiogenic Rats Is Associated With Increased Cavernosal Contraction and Decreased Neuronal Nitric Oxide Synthase Protein Expression. UROLOGY, v. 106, AUG 2017. (10/17362-4, 15/21976-1, 05/56447-7, 16/11988-5)

BOMFIM, GISELE F.; RODRIGUES, FERNANDA LUCIANO; CARNEIRO, FERNANDO S.. Are the innate and adaptive immune systems setting hypertension on fire?. PHARMACOLOGICAL RESEARCH, v. 117, p. 377-393, MAR 2017. (15/21976-1, 10/17362-4, 16/11988-5)

REIS, MOUZARLLEM B.; RODRIGUES, FERNANDA L.; LAUTHERBACH, NATALIA; KANASHIRO, ALEXANDRE; SORGI, CARLOS A.; MEIRELLES, ALYNE F. G.; SILVA, CARLOS A. A.; ZOCCAL, KARINA F.; SOUZA, CAMILA O. S.; RAMOS, SIMONE G.; et al. Interleukin-1 receptor-induced PGE(2) production controls acetylcholine-mediated cardiac dysfunction and mortality during scorpion envenomation. NATURE COMMUNICATIONS, v. 11, n. 1, OCT 28 2020. (15/21976-1, 14/07125-6, 17/02314-3, 15/00658-1)

RODRIGUES, FERNANDA LUCIANO; DA COSTA, RAFAEL MENEZES; AGUIAR SILVA, CARLOS ALBERTO; BOMFIM, GISELE FACHOLI; CARNEIRO, FERNANDO SILVA; TOSTES, RITA; FAZAN JUNIOR, RUBENS; SALGADO, HELIO CESAR. Toll-Like Receptor 9 (TLR9) Is Associated with Vascular Dysfunction in 2-Kydney 1-Clip (2K1C) Hipertensive Mice.. FASEB JOURNAL, v. 32, n. 1, p. 2-pg., 2018-04-01. (15/21976-1, 13/20549-7, 16/11988-5)