Role of the iNOS isoform in the cardiovascular dysfunctions of male rats with 6-OHDA-induced Parkinsonism
Autor(a) principal: | |
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Data de Publicação: | 2023 |
Outros Autores: | , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1016/j.niox.2023.04.003 http://hdl.handle.net/11449/248708 |
Resumo: | Introduction: Available studies have shown the involvement of nitric oxide (NO) in the processes that lead to neurodegeneration in Parkinson's disease (PD). Also, the use of inhibitors of the inducible isoform of NO-synthase (iNOS) promotes neuroprotection and attenuates dopamine (DA) loss in experimental models of Parkinsonism. In addition, NO also appears to be involved in cardiovascular changes in 6-hydroxydopamine (6-OHDA)-induced Parkinsonism. The current study aimed to evaluate the effects of iNOS inhibition on cardiovascular and autonomic function in animals that were subjected to Parkinsonism by the administration of 6-OHDA. Materials and methods: The animals underwent stereotaxic surgery for bilateral microinfusion of the neurotoxin 6-OHDA (6 mg/mL in 0.2% ascorbic acid in sterile saline solution) or vehicle solution for the Sham group. From the day of stereotaxis until the day of femoral artery catheterization, the animals were treated with the iNOS inhibitor, S-methylisothiourea (SMT; 10 mg/kg; i. p.) or saline solution (0.9%; i. p.) for 7 days. The animals were divided into four groups: Sham-Saline, Sham-SMT, 6-OHDA-Saline, and 6-OHDA-SMT. Subsequent analyses were performed on these four groups. After 6 days, they underwent catheterization of the femoral artery, and 24 h later, mean arterial pressure (MAP) and heart rate (HR) were recorded. Another group of animals (the 6-OHDA and Sham groups) was assessed for aortic vascular reactivity after 7 days of bilateral infusion of 6-OHDA or vehicle, in which cumulative concentration-effect curves (CCEC) were made for phenylephrine (Phenyl), acetylcholine and sodium nitroprusside (NPS). Also, CCEC in the presence of Nw-nitro-arginine-methyl-ester (L-NAME) (10-5 M), SMT (10-6 M), and indomethacin (10-5 M) blockers were made. Results: The effectiveness of the 6-OHDA lesion was confirmed with the reduction of DA in 6-OHDA animals. However, treatment with SMT could not reverse the loss of DA. Concerning the baseline parameters, SBP and MAP values were lower in 6-OHDA animals compared to their Sham control, with no effect of treatment with SMT. In the analysis of SBP variability, a decrease in variance, the VLFabs component, and the LFabs component were observed in the 6-OHDA groups when compared to their controls, regardless of treatment with SMT. It was also observed that intravenous injections of SMT resulted in an increase in BP and a decrease in HR. However, the response was not different between the Sham and 6-OHDA groups. In vascular function, there was a hyporeactivity to Phenyl in the 6-OHDA group, and when investigating the mechanisms of this hyporeactivity, it was seen that the Rmax to Phenyl increased with incubation with SMT, indicating that iNOS could be involved in the vascular hyporeactivity of animals with Parkinsonism. Conclusion: Thus, the set of results presented in this study suggests that part of the cardiovascular dysfunction in animals subjected to 6-OHDA Parkinsonism may be peripheral and involve the participation of endothelial iNOS. |
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Role of the iNOS isoform in the cardiovascular dysfunctions of male rats with 6-OHDA-induced ParkinsonismBlood pressureCardiovascular changesNitric oxide synthaseParkinson's diseaseS-methylisothioureaVascular reactivityIntroduction: Available studies have shown the involvement of nitric oxide (NO) in the processes that lead to neurodegeneration in Parkinson's disease (PD). Also, the use of inhibitors of the inducible isoform of NO-synthase (iNOS) promotes neuroprotection and attenuates dopamine (DA) loss in experimental models of Parkinsonism. In addition, NO also appears to be involved in cardiovascular changes in 6-hydroxydopamine (6-OHDA)-induced Parkinsonism. The current study aimed to evaluate the effects of iNOS inhibition on cardiovascular and autonomic function in animals that were subjected to Parkinsonism by the administration of 6-OHDA. Materials and methods: The animals underwent stereotaxic surgery for bilateral microinfusion of the neurotoxin 6-OHDA (6 mg/mL in 0.2% ascorbic acid in sterile saline solution) or vehicle solution for the Sham group. From the day of stereotaxis until the day of femoral artery catheterization, the animals were treated with the iNOS inhibitor, S-methylisothiourea (SMT; 10 mg/kg; i. p.) or saline solution (0.9%; i. p.) for 7 days. The animals were divided into four groups: Sham-Saline, Sham-SMT, 6-OHDA-Saline, and 6-OHDA-SMT. Subsequent analyses were performed on these four groups. After 6 days, they underwent catheterization of the femoral artery, and 24 h later, mean arterial pressure (MAP) and heart rate (HR) were recorded. Another group of animals (the 6-OHDA and Sham groups) was assessed for aortic vascular reactivity after 7 days of bilateral infusion of 6-OHDA or vehicle, in which cumulative concentration-effect curves (CCEC) were made for phenylephrine (Phenyl), acetylcholine and sodium nitroprusside (NPS). Also, CCEC in the presence of Nw-nitro-arginine-methyl-ester (L-NAME) (10-5 M), SMT (10-6 M), and indomethacin (10-5 M) blockers were made. Results: The effectiveness of the 6-OHDA lesion was confirmed with the reduction of DA in 6-OHDA animals. However, treatment with SMT could not reverse the loss of DA. Concerning the baseline parameters, SBP and MAP values were lower in 6-OHDA animals compared to their Sham control, with no effect of treatment with SMT. In the analysis of SBP variability, a decrease in variance, the VLFabs component, and the LFabs component were observed in the 6-OHDA groups when compared to their controls, regardless of treatment with SMT. It was also observed that intravenous injections of SMT resulted in an increase in BP and a decrease in HR. However, the response was not different between the Sham and 6-OHDA groups. In vascular function, there was a hyporeactivity to Phenyl in the 6-OHDA group, and when investigating the mechanisms of this hyporeactivity, it was seen that the Rmax to Phenyl increased with incubation with SMT, indicating that iNOS could be involved in the vascular hyporeactivity of animals with Parkinsonism. Conclusion: Thus, the set of results presented in this study suggests that part of the cardiovascular dysfunction in animals subjected to 6-OHDA Parkinsonism may be peripheral and involve the participation of endothelial iNOS.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Departamento de Ciências Fisiológicas Universidade Estadual de Londrina – UEL, PRDepartamento de Ciências Patológicas Universidade Estadual de Londrina – UEL, PRFaculdade de Ciências Farmacêuticas de Araraquara Departamento de Princípios Ativos Naturais e Toxicologia Universidade Estadual Paulista - UNESPFaculdade de Ciências Farmacêuticas de Araraquara Departamento de Princípios Ativos Naturais e Toxicologia Universidade Estadual Paulista - UNESPUniversidade Estadual de Londrina (UEL)Universidade Estadual Paulista (UNESP)de Jager, LorenaVidigal, Camila Boreckide Campos, Blenda HyedraReginato, Gabriela SouzaFernandes, Lorena MariaAriza, DeborahHigashi-Mckeown, Carolina MatiasBertozzi, Mariana MarquesRasquel de Oliveira, Fernanda SoaresVerri Jr, Waldiceu AparecidoCeravolo, Graziela ScaliantiCrestani, Carlos César [UNESP]Pinge-Filho, PhilenoMartins-Pinge, Marli Cardoso2023-07-29T13:51:25Z2023-07-29T13:51:25Z2023-05-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article49-60http://dx.doi.org/10.1016/j.niox.2023.04.003Nitric Oxide - Biology and Chemistry, v. 134-135, p. 49-60.1089-86111089-8603http://hdl.handle.net/11449/24870810.1016/j.niox.2023.04.0032-s2.0-85152737095Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengNitric Oxide - Biology and Chemistryinfo:eu-repo/semantics/openAccess2023-07-29T13:51:25Zoai:repositorio.unesp.br:11449/248708Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462023-07-29T13:51:25Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Role of the iNOS isoform in the cardiovascular dysfunctions of male rats with 6-OHDA-induced Parkinsonism |
title |
Role of the iNOS isoform in the cardiovascular dysfunctions of male rats with 6-OHDA-induced Parkinsonism |
spellingShingle |
Role of the iNOS isoform in the cardiovascular dysfunctions of male rats with 6-OHDA-induced Parkinsonism de Jager, Lorena Blood pressure Cardiovascular changes Nitric oxide synthase Parkinson's disease S-methylisothiourea Vascular reactivity |
title_short |
Role of the iNOS isoform in the cardiovascular dysfunctions of male rats with 6-OHDA-induced Parkinsonism |
title_full |
Role of the iNOS isoform in the cardiovascular dysfunctions of male rats with 6-OHDA-induced Parkinsonism |
title_fullStr |
Role of the iNOS isoform in the cardiovascular dysfunctions of male rats with 6-OHDA-induced Parkinsonism |
title_full_unstemmed |
Role of the iNOS isoform in the cardiovascular dysfunctions of male rats with 6-OHDA-induced Parkinsonism |
title_sort |
Role of the iNOS isoform in the cardiovascular dysfunctions of male rats with 6-OHDA-induced Parkinsonism |
author |
de Jager, Lorena |
author_facet |
de Jager, Lorena Vidigal, Camila Borecki de Campos, Blenda Hyedra Reginato, Gabriela Souza Fernandes, Lorena Maria Ariza, Deborah Higashi-Mckeown, Carolina Matias Bertozzi, Mariana Marques Rasquel de Oliveira, Fernanda Soares Verri Jr, Waldiceu Aparecido Ceravolo, Graziela Scalianti Crestani, Carlos César [UNESP] Pinge-Filho, Phileno Martins-Pinge, Marli Cardoso |
author_role |
author |
author2 |
Vidigal, Camila Borecki de Campos, Blenda Hyedra Reginato, Gabriela Souza Fernandes, Lorena Maria Ariza, Deborah Higashi-Mckeown, Carolina Matias Bertozzi, Mariana Marques Rasquel de Oliveira, Fernanda Soares Verri Jr, Waldiceu Aparecido Ceravolo, Graziela Scalianti Crestani, Carlos César [UNESP] Pinge-Filho, Phileno Martins-Pinge, Marli Cardoso |
author2_role |
author author author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade Estadual de Londrina (UEL) Universidade Estadual Paulista (UNESP) |
dc.contributor.author.fl_str_mv |
de Jager, Lorena Vidigal, Camila Borecki de Campos, Blenda Hyedra Reginato, Gabriela Souza Fernandes, Lorena Maria Ariza, Deborah Higashi-Mckeown, Carolina Matias Bertozzi, Mariana Marques Rasquel de Oliveira, Fernanda Soares Verri Jr, Waldiceu Aparecido Ceravolo, Graziela Scalianti Crestani, Carlos César [UNESP] Pinge-Filho, Phileno Martins-Pinge, Marli Cardoso |
dc.subject.por.fl_str_mv |
Blood pressure Cardiovascular changes Nitric oxide synthase Parkinson's disease S-methylisothiourea Vascular reactivity |
topic |
Blood pressure Cardiovascular changes Nitric oxide synthase Parkinson's disease S-methylisothiourea Vascular reactivity |
description |
Introduction: Available studies have shown the involvement of nitric oxide (NO) in the processes that lead to neurodegeneration in Parkinson's disease (PD). Also, the use of inhibitors of the inducible isoform of NO-synthase (iNOS) promotes neuroprotection and attenuates dopamine (DA) loss in experimental models of Parkinsonism. In addition, NO also appears to be involved in cardiovascular changes in 6-hydroxydopamine (6-OHDA)-induced Parkinsonism. The current study aimed to evaluate the effects of iNOS inhibition on cardiovascular and autonomic function in animals that were subjected to Parkinsonism by the administration of 6-OHDA. Materials and methods: The animals underwent stereotaxic surgery for bilateral microinfusion of the neurotoxin 6-OHDA (6 mg/mL in 0.2% ascorbic acid in sterile saline solution) or vehicle solution for the Sham group. From the day of stereotaxis until the day of femoral artery catheterization, the animals were treated with the iNOS inhibitor, S-methylisothiourea (SMT; 10 mg/kg; i. p.) or saline solution (0.9%; i. p.) for 7 days. The animals were divided into four groups: Sham-Saline, Sham-SMT, 6-OHDA-Saline, and 6-OHDA-SMT. Subsequent analyses were performed on these four groups. After 6 days, they underwent catheterization of the femoral artery, and 24 h later, mean arterial pressure (MAP) and heart rate (HR) were recorded. Another group of animals (the 6-OHDA and Sham groups) was assessed for aortic vascular reactivity after 7 days of bilateral infusion of 6-OHDA or vehicle, in which cumulative concentration-effect curves (CCEC) were made for phenylephrine (Phenyl), acetylcholine and sodium nitroprusside (NPS). Also, CCEC in the presence of Nw-nitro-arginine-methyl-ester (L-NAME) (10-5 M), SMT (10-6 M), and indomethacin (10-5 M) blockers were made. Results: The effectiveness of the 6-OHDA lesion was confirmed with the reduction of DA in 6-OHDA animals. However, treatment with SMT could not reverse the loss of DA. Concerning the baseline parameters, SBP and MAP values were lower in 6-OHDA animals compared to their Sham control, with no effect of treatment with SMT. In the analysis of SBP variability, a decrease in variance, the VLFabs component, and the LFabs component were observed in the 6-OHDA groups when compared to their controls, regardless of treatment with SMT. It was also observed that intravenous injections of SMT resulted in an increase in BP and a decrease in HR. However, the response was not different between the Sham and 6-OHDA groups. In vascular function, there was a hyporeactivity to Phenyl in the 6-OHDA group, and when investigating the mechanisms of this hyporeactivity, it was seen that the Rmax to Phenyl increased with incubation with SMT, indicating that iNOS could be involved in the vascular hyporeactivity of animals with Parkinsonism. Conclusion: Thus, the set of results presented in this study suggests that part of the cardiovascular dysfunction in animals subjected to 6-OHDA Parkinsonism may be peripheral and involve the participation of endothelial iNOS. |
publishDate |
2023 |
dc.date.none.fl_str_mv |
2023-07-29T13:51:25Z 2023-07-29T13:51:25Z 2023-05-01 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.1016/j.niox.2023.04.003 Nitric Oxide - Biology and Chemistry, v. 134-135, p. 49-60. 1089-8611 1089-8603 http://hdl.handle.net/11449/248708 10.1016/j.niox.2023.04.003 2-s2.0-85152737095 |
url |
http://dx.doi.org/10.1016/j.niox.2023.04.003 http://hdl.handle.net/11449/248708 |
identifier_str_mv |
Nitric Oxide - Biology and Chemistry, v. 134-135, p. 49-60. 1089-8611 1089-8603 10.1016/j.niox.2023.04.003 2-s2.0-85152737095 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Nitric Oxide - Biology and Chemistry |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
49-60 |
dc.source.none.fl_str_mv |
Scopus reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
|
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1799964784182951936 |