Role of carotid chemoreceptors in hemodynamic and ventilatory responses to electrical stimulation of the carotid sinus and effects of its chronic inhibition in the development of hypertension in Spontaneously Hypertensive Rats (SHR)

• Grant number: 15/18511-7
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: January 01, 2016
• End date: March 31, 2018
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Helio Cesar Salgado
• Grantee: Pedro Lourenço Katayama
• 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
• Associated scholarship(s): 16/02184-0 - P2X3 receptor targeting in the carotid body for regulating hypertension: a translational perspective, BE.EP.DD

Abstract

The role of the carotid body in the context of cardiovascular diseases has been widely explored. In a recently published study (Hypertension 66: 598-603, 2015) our laboratory demonstrated that carotid body attenuate the hypotensive response to electrical stimulation of the carotid sinus/carotid sinus nerve in conscious rats. Although a recent clinical study has been suggested that electrical stimulation of the carotid sinus in patients does not lead to carotid body activation because ventilatory alterations were not observed, the mechanisms involved in this therapeutic approach requires thorough investigation. Thus, the aim of the first part of the current project is to investigate the ventilatory responses to electrical stimulation of the carotid sinus/carotid sinus nerve in conscious rats. Moreover, recent evidence has been shown that carotid body contributes significantly to the sympathoexcitation that occurs in hypertension. Thus, the carotid body emerges as a new target in the treatment of this disease. Researchers at the University of Bristol demonstrated that acute pharmacological inhibition of carotid body in Spontaneously Hypertensive Rats (SHR) reduced the arterial pressure. Therefore, a collaboration with the researchers mentioned above is being proposed to investigate the effects of chronic pharmacological carotid body inhibition in the development and maintenance of hypertension in SHR. For this, normotensive rats and SHR will be chronically treated with a new selective antagonist for P2X3 subunit of purinergic receptors (AF-130). P2X3 receptors are involved in the chemical transduction that occurs in the carotid body. During treatment, hemodynamic parameters and sympathetic renal nerve activity will be measured. After, the animals will be subjected to carotid body ablation to verify whether the treatment effects on hemodynamic parameters and sympathetic renal nerve activity are dependent on carotid body mediation. Furthermore, western blot and immunohistochemistry techniques will be applied to the carotid bodies and petrosal ganglia from normotensive rats and SHR, and also from normotensive and hypertensive patients post-mortem. The objectives of these protocols are to examine the expression and localization of P2X3 receptors. (AU)

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)

CASTANIA, JACI A.; KATAYAMA, PEDRO L.; BROGNARA, FERNANDA; MORAES, DAVI J. A.; SABINO, JOAO PAULO J.; SALGADO, HELIO C.. Selective denervation of the aortic and carotid baroreceptors in rats. Experimental Physiology, v. 104, n. 9, p. 1335-1342, SEP 2019. (17/05163-6, 13/10484-5, 13/20549-7, 15/18511-7)

KATAYAMA, PEDRO L.; CASTANIA, JACI A.; FAZAN JR, RUBENS; SALGADO, HELIO C.. Interaction between baroreflex and chemoreflex in the cardiorespiratory responses to stimulation of the carotid sinus/nerve in conscious rats. AUTONOMIC NEUROSCIENCE-BASIC & CLINICAL, v. 216, p. 17-24, JAN 2019. (15/18511-7)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

KATAYAMA, Pedro Lourenço. Role of carotid chemoreceptors in hemodynamic and respiratory responses to electrical stimulation of the carotid sinus/carotid sinus nerve. 2018. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC) Ribeirão Preto.