Involvement of the Angiotensin II / AT1 receptor angiotensin 1-7 / Mas receptor signaling in the medial nucleus of the amygdala in the cardiovascular and anxiogenic responses to stress in rats

• Grant number: 16/05218-2
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: October 01, 2016
• End date: June 30, 2020
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Carlos Cesar Crestani
• Grantee: Willian Costa Ferreira
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

Studies in humans and animals have provided evidence linking stress and the pathogenesis of various cardiovascular complications and psychiatric disorders, such as anxiety. Despite the relevance of these findings, the neurobiological mechanisms involved in cardiovascular and behavioral changes induced by stress are still poorly understood. The amygdaloid complex is an important limbic structure involved in the physiological and behavioral responses to stress. One of the subnucleus of amigdaloide complex activated during stress is the medial nucleus (MeA). Indeed, it has been shown the involvement of MeA on cardiovascular responses and anxiogenic effect of stress. However, the local neurochemical mechanisms involved in the control of these responses are still poorly understood. Angiotensin II acting on the AT1 receptor has been shown to be an important signaling mechanism in the central nervous system involved in the etiology of behavioral changes and physiological adjustments observed during exposure to aversive stimuli. Data also showed that exposure to stress causes changes in the formation of angiotensin II in the central nervous system. In addition, recent data demonstrated that angiotensin 1-7/Mas receptor signaling, a counter-regulatory mechanism of angiotensin II in the renin-angiotensin system (RAS), play an inhibitory role in stress-evoked responses. Despite these pieces of evidence, the specific sites in the brain where the angiotensin II and angiotensin 1-7 act to control stress responses are not completely known. Angiotensinergic terminals and RAS components were identified in the MeA. However, a possible involvement of RAS in MeA in cardiovascular and anxiogenic responses induced by stress was never investigated. Thus, our proposal in this study is: 1) to investigate the involvement of angiotensin II/AT1 receptor and angiotensin 1-7/Mas receptor signaling mechanisms in the MeA on cardiovascular responses and anxiogenic effect induced by acute restraint stress in rats; 2) to evaluate the effect of prior repeated exposure to restraint stress in control of cardiovascular and anxiogenic responses to restraint stress by angiotensin II/AT1 receptor and angiotensin 1-7/Mas receptor in the MeA in rats; 3) to investigate the involvement of angiotensin II/AT1 receptor and angiotensin 1-7/Mas receptor signaling MeA changes in chantes on cardiovascular basal parameters and baroreflex activity induced by repeated exposure to restraint stress in rats; and 4) to evaluate the effect of repeated exposure to restraint stress on the protein levels of AT1 and Mas receptors in the MeA in rats. (AU)

Scientific publications

(5)

(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)

MARCHI-COELHO, CAMILA; COSTA-FERREIRA, WILLIAN; REIS-SILVA, LILIAN L.; CRESTANI, CARLOS C.. Angiotensinergic Neurotransmissions in the Medial Amygdala Nucleus Modulate Behavioral Changes in the Forced Swimming Test Evoked by Acute Restraint Stress in Rats. CELLS, v. 10, n. 5, MAY 2021. (18/23686-9, 19/24478-3, 16/05218-2)

GOMES-DE-SOUZA, LUCAS; COSTA-FERREIRA, WILLIAN; MENDONCA, MICHELLE M.; XAVIER, CARLOS H.; CRESTANI, CARLOS C.. Lateral hypothalamus involvement in control of stress response by bed nucleus of the stria terminalis endocannabinoid neurotransmission in male rats. SCIENTIFIC REPORTS, v. 11, n. 1, AUG 9 2021. (16/05028-9, 16/05218-2, 19/24478-3, 17/19249-0)

COSTA-FERREIRA, WILLIAN; GOMES-DE-SOUZA, LUCAS; CRESTANI, CARLOS C.. AT(2) and MAS (but not AT(1)) angiotensinergic receptors in the medial amygdaloid nucleus modulate the baroreflex activity in rats. PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, v. 471, n. 9, p. 1173-1182, SEP 2019. (15/05922-9, 16/05218-2, 17/19249-0)

GOMES-DE-SOUZA, LUCAS; BENINI, RICARDO; COSTA-FERREIRA, WILLIAN; CRESTANI, CARLOS C.. GAB(A) but not GABA(B) receptors in the lateral hypothalamus modulate the tachycardic response to emotional stress in rats. European Neuropsychopharmacology, v. 29, n. 5, p. 672-680, MAY 2019. (15/05922-9, 16/05218-2, 16/05028-9, 17/19249-0)

GOMES-DE-SOUZA, LUCAS; BIANCHI, PAULA C.; COSTA-FERREIRA, WILLIAN; TOMEO, RODRIGO A.; CRUZ, FABIO C.; CRESTANI, CARLOS C.. CB1 and CB2 receptors in the bed nucleus of the stria terminalis differently modulate anxiety-like behaviors in rats. PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY, v. 110, AUG 30 2021. (16/05028-9, 16/05218-2)