The AT-1 Angiotensin Receptor is Involved in the Autonomic and Neuroendocrine Responses to Acute Restraint Stress in Male Rats

Autor(es)

Brasil, Taiz F. S. ^[1] ; Belem-Filho, Ivaldo J. A. ^[1] ; Fortaleza, Eduardo A. T. ^[1] ; Antunes-Rodrigues, Jose ^[2] ; Correa, Fernando M. A. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Pharmacol, Ave Bandeirantes, BR-39001404 Ribeirao Preto - Brazil

^[2] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Physiol, Ribeirao Preto, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Cellular and Molecular Neurobiology; v. 42, n. 1, SI, p. 109-124, JAN 2022.
• Citações Web of Science: 0

Resumo

The renin-angiotensin system (RAS) is involved in cardiovascular and hydroelectrolytic control, being associated with the development of hypertension. The restraint stress (RS) model is an aversive situation, which promotes a sustained increase in blood pressure and heart rate, and stimulation of the hypothalamic-pituitary-adrenal axis. Stress leads to an increase of angiotensin-II contents both in the circulation and the central nervous system (CNS), as well as an increased expression of AT-1 receptors in CNS structures related to stress. Stressful stimuli are associated with the modulation of autonomic nervous system, as well as baroreflex; changes in this adjustment mechanism are related to cardiovascular diseases. We hypothesized that RAS is involved in the modulation of autonomic, neuroendocrine, and functional RS-caused alterations. The intravenous (i.v) pretreatment of rats with lisinopril, an angiotensin-converting-enzyme inhibitor, reduced the RS-evoked pressor response. The doses of 0.1 and 0.3 mg/kg also reduced the RS-evoked tachycardia, while in the dose of 1 mg/kg of lisinopril potentiated the tachycardic one. Additionally, i.v. pretreatment with losartan, a selective AT-1 receptor antagonist, reduced the pressor and the tachycardic responses caused by RS. Pretreatment with lisinopril 0.3 mg/kg increased the power of the low frequency (LF) band of the systolic BP spectrum after the treatment without affecting this parameter during RS. The pretreatment with losartan 1 mg/kg increased the power of the high frequency (HF) band and reduced the LF (n.u.) and the LF/HF ratio of the pulse interval spectrum in the first hour of RS. Concerning baroreflex sensitiveness (SBR), pretreatments with losartan or lisinopril did not affect the gain of the baroreflex sequences. However, the pretreatment with losartan reduced the baroreflex effectiveness index of the total sequences in the third hour of the RS. These results indicate that Ang-II, via the AT-1 receptor, plays a facilitating influence on the cardiovascular response caused by RS; facilitates sympathetic activation and reduces parasympathetic activity related to RS; facilitates the baroreflex activation during RS and favors corticosterone release under this stress model. The impairment of Ang-II synthesis, as well as the blockade of AT-1 receptors, may constitute an important pharmacological strategy to treat cardiovascular consequences caused by stress. (AU)

• Processo FAPESP: 12/18556-2 - Envolvimento do sistema glutamatérgico dos núcleos paraventricular e supra-óptico na modulação do sistema cardiovascular e na liberação de vasopressina e ocitocina em ratos submetidos ao estímulo osmótico.
• Beneficiário: Eduardo Albino Trindade Fortaleza
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 16/25502-7 - Efeitos cardiovasculares, comportamentais, neuroendócrinos e morfofuncionais evocados pelo estresse agudo por restrição em ratos: envolvimento da via ocitocinérgica
• Beneficiário: Ivaldo de Jesus Almeida Belém Filho
• Modalidade de apoio: Bolsas no Brasil - Doutorado