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Involvement of angiotensinergic neurotransmissions of medial amygdaloid nucleus in control of cardiovascular and anxiogenic responses to stress in rats.

Grant number: 17/19249-0
Support Opportunities:Regular Research Grants
Start date: February 01, 2018
End date: January 31, 2020
Field of knowledge:Biological Sciences - Pharmacology - Neuropsychopharmacology
Principal Investigator:Carlos Cesar Crestani
Grantee:Carlos Cesar Crestani
Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

Clinical and preclinical studies have provided evidence linking stress and the pathogenesis of various cardiovascular complications and psychiatric disorders. Despite the relevance of these findings, the neurobiological mechanisms involved in cardiovascular and behavioral changes evoked by stress are still poorly understood. The amygdaloid complex is an important limbic structure involved in the physiological and behavioral responses to stress. A subnucleus of amigdaloide complex activated during stress is the medial nucleus (MeA). Indeed, it has been shown an 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 neurochemical mechanism in the central nervous system involved in the etiology of behavioral changes and physiological adjustments 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 during an acute session of restraint stress in male 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 of male rats; 3) to investigate the involvement of angiotensin II/AT1 receptor and angiotensin 1-7/Mas receptor signaling MeA changes in changes on cardiovascular basal parameters and baroreflex activity induced by repeated exposure to restraint stress in male 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 male rats. (AU)

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Scientific publications (21)
(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)
VIEIRA, JONAS O.; DUARTE, JOSIANE O.; COSTA-FERREIRA, WILLIAN; CRESTANI, CARLOS C.. Influence of pre-existing hypertension on neuroendocrine and cardiovascular changes evoked by chronic stress in female rats. PSYCHONEUROENDOCRINOLOGY, v. 97, p. 111-119, . (17/19249-0, 15/05922-9)
BENINI, RICARDO; OLIVEIRA, LEANDRO A.; GOMES-DE-SOUZA, LUCAS; CRESTANI, CARLOS C.. Habituation of the cardiovascular responses to restraint stress in male rats: influence of length, frequency and number of aversive sessions. STRESS-THE INTERNATIONAL JOURNAL ON THE BIOLOGY OF STRESS, v. 22, n. 1, p. 151-161, . (17/19249-0, 15/05922-9)
COSTA-FERREIRA, WILLIAN; GOMES-DE-SOUZA, LUCAS; CRESTANI, CARLOS C.. Role of angiotensin receptors in the medial amygdaloid nucleus in autonomic, baroreflex and cardiovascular changes evoked by chronic stress in rats. European Journal of Neuroscience, v. 53, n. 3, . (15/05922-9, 17/19249-0)
SANTOS, CARLOS E.; BENINI, RICARDO; CRESTANI, CARLOS C.. Spontaneous recovery, time course, and circadian influence on habituation of the cardiovascular responses to repeated restraint stress in rats. PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, v. 472, n. 10, . (15/05922-9, 17/19249-0)
TOMEO, RODRIGO A.; GOMES-DE-SOUZA, LUCAS; BENINI, RICARDO; REIS-SILVA, LILIAN L.; CRESTANI, CARLOS C.. Site-Specific Regulation of Stress Responses Along the Rostrocaudal Axis of the Insular Cortex in Rats. FRONTIERS IN NEUROSCIENCE, v. 16, p. 12-pg., . (19/24478-3, 17/19249-0)
BARRETTO-DE-SOUZA, LUCAS; BENINI, RICARDO; REIS-SILVA, LILIAN L.; CRESTANI, CARLOS C.. Corticotropin-releasing factor neurotransmission in the lateral hypothalamus modulates the tachycardiac response during acute emotional stress in rats. Brain Research Bulletin, v. 166, p. 102-109, . (17/19249-0)
XAVIER, CARLOS HENRIQUE; DE MENEZES, RODRIGO CUNHA ALVIM; CHIANCA, DEOCLECIO ALVES; FONTES, MARCO ANTONIO PELIKY; CRESTANI, CARLOS CESAR. Editorial: Stress-Related Diseases and Dysfunctions. FRONTIERS IN PHYSIOLOGY, v. 13, p. 3-pg., . (17/19249-0, 19/24478-3)
GOULART, MELISSA T.; BUSNARDO, CRISTIANE; BELEM-FILHO, IVALDO J. A.; BENINI, RICARDO; FASSINI, ALINE; CRESTANI, CARLOS C.; GODOY, ANA C.; CORREA, FERNANDO M. A.; ALVES, FERNANDO H. F.. NMDA receptors in the insular cortex modulate cardiovascular and autonomic but not neuroendocrine responses to restraint stress in rats. PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY, v. 119, p. 10-pg., . (21/00148-4, 18/04899-1, 15/05922-9, 17/19249-0)
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, . (16/05028-9, 16/05218-2, 19/24478-3, 17/19249-0)
OLIVEIRA, LEANDRO A.; GOMES-DE-SOUZA, LUCAS; BENINI, RICARDO; WOOD, SUSAN K.; CRESTANI, CARLOS C.. Both CRF1 and CRF2 receptors in the bed nucleus of stria terminalis are involved in baroreflex impairment evoked by chronic stress in rats. PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY, v. 105, . (17/19249-0, 15/05922-9)
REIS-SILVA, LILIAN L.; BARRETTO-DE-SOUZA, LUCAS; BENINI, RICARDO; CRESTANI, CARLOS C.. CRF1 and CRF2 receptors in the lateral hypothalamus differently modulate the baroreflex function in unanesthetized rats. Brain Research, v. 1751, . (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, . (15/05922-9, 16/05218-2, 16/05028-9, 17/19249-0)
ALMEIDA, JEFERSON; OLIVEIRA, LEANDRO A.; BENINI, RICARDO; CRESTANI, CARLOS C.. Role of hippocampal nitrergic neurotransmission in behavioral and cardiovascular dysfunctions evoked by chronic social stress. NITRIC OXIDE-BIOLOGY AND CHEMISTRY, v. 94, p. 114-124, . (15/05922-9, 17/19249-0)
COSTA-FERREIRA, MILIAN; MORAIS-SILVA, GESSYNGER; GOMES-DE-SOUZA, LUCAS; MARIN, MARCELO T.; CRESTANI, CARLOS C.. The AT1 Receptor Antagonist Losartan Does Not Affect Depressive-Like State and Memory Impairment Evoked by Chronic Stressors in Rats. FRONTIERS IN PHARMACOLOGY, v. 10, . (15/05922-9, 17/19249-0)
MORENO-SANTOS, BEATRIZ; MARCHI-COELHO, CAMILA; COSTA-FERREIRA, WILLIAN; CRESTANI, CARLOS C.. Angiotensinergic receptors in the medial amygdaloid nucleus differently modulate behavioral responses in the elevated plus-maze and forced swimming test in rats. Behavioural Brain Research, v. 397, . (17/19249-0)
ALMEIDA, JEFERSON; OLIVEIRA, LEANDRO A.; BENINI, RICARDO; CRESTANI, CARLOS C.. Differential roles of hippocampal nNOS and iNOS in the control of baroreflex function in conscious rats. Brain Research, v. 1710, p. 109-116, . (17/19249-0, 15/05922-9)
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, . (15/05922-9, 16/05218-2, 17/19249-0)
BENINI, RICARDO; OLIVEIRA, LEANDRO A.; GOMES-DE-SOUZA, LUCAS; RODRIGUES, BRUNO; CRESTANI, CARLOS C.. Habituation of the cardiovascular response to restraint stress is inhibited by exposure to other stressor stimuli and exercise training. Journal of Experimental Biology, v. 223, n. 8, . (15/05922-9, 17/19249-0)
BARRETTO-DE-SOUZA, LUCAS; BENINI, RICARDO; REIS-SILVA, LILIAN LIZ; CRESTANI, CARLOS C.. Role of CRF1 and CRF2 receptors in the lateral hypothalamus in cardiovascular and anxiogenic responses evoked by restraint stress in rats: Evaluation of acute and chronic exposure. Neuropharmacology, v. 212, p. 14-pg., . (17/19249-0, 19/24478-3)
CRESTANI, CARLOS C.; TOMEO, RODRIGO A.; GOMES-DE-SOUZA, LUCAS; BENINI, RICARDO; REIS-SILVA, LILIAN L.. Site-specific regulation of emotional stress responses along the rostrocaudal axis of the insular cortex in rats. FASEB JOURNAL, v. 36, p. 1-pg., . (19/24478-3, 17/19249-0)