Recuperação cardiovascular induzida por infusão de solução salina hipertônica em ratos hemorrágicos: participação dos receptores adrenérgicos no órgão subfornical

• Ano de defesa: 2021
• Autor(a) principal: Silva, Amanda Barbosa Coelho da
• Orientador(a): Pedrino, Gustavo Rodrigues
• Banca de defesa: Pedrino, Gustavo Rodrigues, Fajemiroye, James Oluwagbamigbe, Mourão, Aline Andrade, Custodio, Carlos Henrique Xavier
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Goiás
• Programa de Pós-Graduação: Programa de Pós-graduação em Ciências Biológicas (ICB)
• Departamento: Instituto de Ciências Biológicas - ICB (RG)
• País: Brasil
• Palavras-chave em Português: Hiperosmolaridade; Hipotensão; Pressão arterial; Neurotransmissão; Receptores β-adrernérgicos
• Palavras-chave em Inglês: Hyperosmolarity; Hypotension; Blood pressure; Neurotransmission; β-adrenergic receptors
• Área do conhecimento CNPq: CIENCIAS BIOLOGICAS::FARMACOLOGIA::NEUROPSICOFARMACOLOGIA
• Link de acesso: http://repositorio.bc.ufg.br/tede/handle/tede/11992

Previous studies have shown that the immediate restoration of cardiovascular parameters, such as blood pressure and cardiac output, by hypertonic saline solution (HSS) is useful in the treatment of hypotensive hemorrhage (HH). The Subfornical Organ (SFO) receives projections of regions involved in osmotic and cardiovascular control, and the integration of these neuronal regulatory pathways by SFO is assumed to play a role in SSH-induced cardiovascular recovery in hemorrhagic rats. Thus, the present study assessed the role of SFO and adrenergic pathways in cardiovascular responses to HSS infusion in hemorrhagic rats. All experiments were approved by the Ethics Committee on the Use of Animals at the Federal University of Goiás (CEUA-UFG; protocol nº 034/12). Wistar rats (270–300g) were anesthetized with halothane (2% in 98% O2; Tanohalo; Cristália, Itapira, SP, Brazil) and after insertion of the venous catheter, anesthesia was maintained by urethane (1.2 g ∙ kg- 1, iv; Sigma-Aldrich, MO, USA). The animals were instrumented to record mean arterial pressure (MAP), heart rate (HR), renal blood flow (RBF) and aortic (ABF). The values of renal vascular conductance (RCV) and aortic (AVC) were calculated from the ratio between RBF or RBA and MAP, respectively. The HH was induced by withdrawing blood over 10 min until MAP reached approximately 60 mmHg, after which this MAP level was maintained for another 10 minutes by withdrawing or reinfusing blood when necessary. After 10 min of blood withdrawal, saline (NaCl; 0.15M; CONT; n = 5), muscimol (4mM; MUSC; GABAergic agonist; n = 6) or propranolol (10mM; PROP; non-selective β-adrenergic blocker; n = 6) were nanoinjected (100nL) in SFO. The sodium overload, through the infusion of HSS (NaCl 3 M; 1.8 ml ∙ kg-1 of body mass), was performed 20 min after the HH. The HH promoted hypotension (CONT: from 103.3 ± 3.5 to 62 ± 0.3 mmHg; MUSC: from 108 ± 4.4 to 61 ± 0.8 mmHg and PROP: from 98.4 ± 2, 4 to 61 ± 1.3 mmHg; 20 min after HH; p <0.05). The sodium overload promoted MAP restoration to values close to baseline in the animals that received saline nanoinjections (92 ± 3.1 mmHg; 40 min after HSS infusion; p <0.05). However, in animals that received nanoinjections of muscimol and propranolol, the HSS infusion did not restore this parameter to baseline levels (MUSC: 53.0 ± 3.8 mmHg and PROP: 59 ± 4.8 mmHg; 40 min after HSS infusion; p <0.05; compared to baseline). The changes in HR values were not significant in all the groups (CONT: from 402.9 ± 13.4 bpm to 381.0 ± 17.1; MUSC: from 408.0 ± 10.5 bpm to 375.0 ± 22.3 bpm and PROP: from 410 ± 15.6 to 362 ± 14.6 bpm; 20 min after HH). After 40 minutes of HSS infusion, there is no significant change in this parameter (CONT: 346.0 ± 19.7 bpm; MUSC: 352.0 ± 18.1 bpm and PROP: 336.9 ± 14.2 bpm). The HH promoted a significant reduction in RBF in all groups (CONT: ∆: -59.8 ± 5.3%; MUSC: ∆: -53.4 ± 14.6% and PROP: ∆: 48.7 ± 6.8%, in relation to the baseline, p <0.05; 20 minutes after HH). The HSS infusion did not restore the RBF values in the control and experimental groups (CONT: ∆: -20.8 ± 19.1%; MUSC: ∆: -64.9 ± 4.1% and PROP: ∆: -51.3 ± 11.6%, in relation to baseline, p <0.05; 40 minutes after HSS infusion). The was no significant differences in the value of RVC after HH (CONT: ∆: -33.6 ± 8%; MUSC: ∆: -23 ± 6.8% and PROP: 17: -17.4 ± 10.3%, 20 min after HH) and HSS infusion (CONT: ∆: -32.6 ± 2.9%; MUSC: ∆: -27 ± 8.0% and PROP: ∆: - 14.5 ± 15.7%; 40 minutes after HSS infusion). The HH significantly reduced the ABF in the groups (CONT: ∆: -75 ± 5.2%; MUSC: ∆: -60.1 ± 9.0 and PROP: ∆: -57 ± 5%, p <0.05; 20 min after HH), and this reduction was maintained even after 40 minutes of the HSS infusion (CONT; ∆: - 55 ± 5.8%; MUSC: ∆: -57 ± 6.9% and PROP: ∆: -60 ± 3.7% compared to baseline, 40 min after HSS infusion). No changes were observed in the AVC after HH (CONT: ∆: -46.4 ± 14.1%; MUSC: ∆: -30.3 ± 15.1% and PROP: ∆: -30.4 ± 7.4%, p <0.05; 20 min after HH) and HSS infusion (CONT: ∆: -52.2 ± 4.5%; MUSC: ∆: -11.4 ± 14.8 % and PROP: ∆: -33.6 ± 4.1%, 40 minutes after HSS infusion; in relation to baseline). These findings strengthen the hypothesis of the SFO involvement in HSS-induced cardiovascular recovery during HH, and suggest the attenuation of this recovery by pharmacological blockade of β-adrenergic neurotransmission. In this manner, the dysfunction of adrenergic neurotransmission in SFO could prevent HSS-induced cardiovascular recovery after HH.