Chronic treatment with ivabradine does not affect cardiovascular autonomic control in rats.
Autor(a) principal: | |
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Data de Publicação: | 2016 |
Outros Autores: | , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UFOP |
Texto Completo: | http://www.repositorio.ufop.br/handle/123456789/9531 https://doi.org/10.3389/fphys.2016.00305 |
Resumo: | A low resting heart rate (HR) would be of great benefit in cardiovascular diseases. Ivabradine-a novel selective inhibitor of hyperpolarization-activated cyclic nucleotide gated (HCN) channels- has emerged as a promising HR lowering drug. Its effects on the autonomic HR control are little known. This study assessed the effects of chronic treatment with ivabradine on the modulatory, reflex and tonic cardiovascular autonomic control and on the renal sympathetic nerve activity (RSNA). Male Wistar rats were divided in 2 groups, receiving intraperitoneal injections of vehicle (VEH) or ivabradine (IVA) during 7 or 8 consecutive days. Rats were submitted to vessels cannulation to perform arterial blood pressure (AP) and HR recordings in freely moving rats. Time series of resting pulse interval and systolic AP were used to measure cardiovascular variability parameters. We also assessed the baroreflex, chemoreflex and the Bezold-Jarish reflex sensitivities. To better evaluate the effects of ivabradine on the autonomic control of the heart, we performed sympathetic and vagal autonomic blockade. As expected, ivabradine-treated rats showed a lower resting (VEH: 362 ± 16 bpm vs. IVA: 260 ± 14 bpm, p = 0.0005) and intrinsic HR (VEH: 369 ± 9 bpm vs. IVA: 326 ± 11 bpm, p = 0.0146). However, the chronic treatment with ivabradine did not change normalized HR spectral parameters LF (nu) (VEH: 24.2 ± 4.6 vs. IVA: 29.8 ± 6.4; p > 0.05); HF (nu) (VEH: 75.1 ± 3.7 vs. IVA: 69.2 ± 5.8; p > 0.05), any cardiovascular reflexes, neither the tonic autonomic control of the HR (tonic sympathovagal index; VEH: 0.91± 0.02 vs. IVA: 0.88 ± 0.03, p = 0.3494). We performed the AP, HR and RSNA recordings in urethane-anesthetized rats. The chronic treatment with ivabradine reduced the resting HR (VEH: 364 ± 12 bpm vs. IVA: 207 ± 11 bpm, p < 0.0001), without affecting RSNA (VEH: 117 ± 16 vs. IVA: 120 ± 9 spikes/s, p = 0.9100) and mean arterial pressure (VEH: 70 ± 4 vs. IVA: 77 ± 6 mmHg, p = 0.3293). Our results suggest that, in health rats, the long-term treatment with ivabradine directly reduces the HR without changing the RSNA modulation and the reflex and tonic autonomic control of the heart. |
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Silva, Fernanda Cacilda dos SantosPaiva, Franciny AparecidaRibeiro, Flavia Camargos de Figueiredo MüllerCaldeira, Henrique Martins ArantesFontes, Marco Antônio PelikyMenezes, Rodrigo Cunha Alvim deCasali, Karina RabelloFortes, Gláucia HelenaTobaldini, EleonoraSolbiati, MonicaMontano, NicolaSilva, Valdo José Dias daChianca Júnior, Deoclécio Alves2018-02-15T12:04:22Z2018-02-15T12:04:22Z2016SILVA, F. C. dos et al. Chronic treatment with ivabradine does not affect cardiovascular autonomic control in rats. Frontiers in Physiology, v. 7, p. 1-10, 2016. Disponível em: <http://journal.frontiersin.org/article/10.3389/fphys.2016.00305/full>. Acesso em: 15 set. 2017.1664-042Xhttp://www.repositorio.ufop.br/handle/123456789/9531https://doi.org/10.3389/fphys.2016.00305A low resting heart rate (HR) would be of great benefit in cardiovascular diseases. Ivabradine-a novel selective inhibitor of hyperpolarization-activated cyclic nucleotide gated (HCN) channels- has emerged as a promising HR lowering drug. Its effects on the autonomic HR control are little known. This study assessed the effects of chronic treatment with ivabradine on the modulatory, reflex and tonic cardiovascular autonomic control and on the renal sympathetic nerve activity (RSNA). Male Wistar rats were divided in 2 groups, receiving intraperitoneal injections of vehicle (VEH) or ivabradine (IVA) during 7 or 8 consecutive days. Rats were submitted to vessels cannulation to perform arterial blood pressure (AP) and HR recordings in freely moving rats. Time series of resting pulse interval and systolic AP were used to measure cardiovascular variability parameters. We also assessed the baroreflex, chemoreflex and the Bezold-Jarish reflex sensitivities. To better evaluate the effects of ivabradine on the autonomic control of the heart, we performed sympathetic and vagal autonomic blockade. As expected, ivabradine-treated rats showed a lower resting (VEH: 362 ± 16 bpm vs. IVA: 260 ± 14 bpm, p = 0.0005) and intrinsic HR (VEH: 369 ± 9 bpm vs. IVA: 326 ± 11 bpm, p = 0.0146). However, the chronic treatment with ivabradine did not change normalized HR spectral parameters LF (nu) (VEH: 24.2 ± 4.6 vs. IVA: 29.8 ± 6.4; p > 0.05); HF (nu) (VEH: 75.1 ± 3.7 vs. IVA: 69.2 ± 5.8; p > 0.05), any cardiovascular reflexes, neither the tonic autonomic control of the HR (tonic sympathovagal index; VEH: 0.91± 0.02 vs. IVA: 0.88 ± 0.03, p = 0.3494). We performed the AP, HR and RSNA recordings in urethane-anesthetized rats. The chronic treatment with ivabradine reduced the resting HR (VEH: 364 ± 12 bpm vs. IVA: 207 ± 11 bpm, p < 0.0001), without affecting RSNA (VEH: 117 ± 16 vs. IVA: 120 ± 9 spikes/s, p = 0.9100) and mean arterial pressure (VEH: 70 ± 4 vs. IVA: 77 ± 6 mmHg, p = 0.3293). Our results suggest that, in health rats, the long-term treatment with ivabradine directly reduces the HR without changing the RSNA modulation and the reflex and tonic autonomic control of the heart.Os trabalho publicados nos websites Frontiers, exceto onde identificado, estão sob uma licença Creative Commons que permite copiar, distribuir e transmitir o trabalho desde que sejam citados o autor e o licenciante. Fonte: Frontiers <https://www.frontiersin.org/legal/copyright-statement>. Acesso em: 27 fev. 2020.info:eu-repo/semantics/openAccessRenal sympathetic nerve activityCardiovascular reflexesTonic controlVagal ActivityChronic treatment with ivabradine does not affect cardiovascular autonomic control in rats.info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleengreponame:Repositório Institucional da UFOPinstname:Universidade Federal de Ouro Preto (UFOP)instacron:UFOPLICENSElicense.txtlicense.txttext/plain; charset=utf-8924http://www.repositorio.ufop.br/bitstream/123456789/9531/2/license.txt62604f8d955274beb56c80ce1ee5dcaeMD52ORIGINALARTIGO_ChronicTreatmentIvabradine.pdfARTIGO_ChronicTreatmentIvabradine.pdfapplication/pdf982616http://www.repositorio.ufop.br/bitstream/123456789/9531/1/ARTIGO_ChronicTreatmentIvabradine.pdfb10ed6fc81752d1aef782625c791710eMD51123456789/95312020-03-11 11:18:17.246oai:localhost: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ório InstitucionalPUBhttp://www.repositorio.ufop.br/oai/requestrepositorio@ufop.edu.bropendoar:32332020-03-11T15:18:17Repositório Institucional da UFOP - Universidade Federal de Ouro Preto (UFOP)false |
dc.title.pt_BR.fl_str_mv |
Chronic treatment with ivabradine does not affect cardiovascular autonomic control in rats. |
title |
Chronic treatment with ivabradine does not affect cardiovascular autonomic control in rats. |
spellingShingle |
Chronic treatment with ivabradine does not affect cardiovascular autonomic control in rats. Silva, Fernanda Cacilda dos Santos Renal sympathetic nerve activity Cardiovascular reflexes Tonic control Vagal Activity |
title_short |
Chronic treatment with ivabradine does not affect cardiovascular autonomic control in rats. |
title_full |
Chronic treatment with ivabradine does not affect cardiovascular autonomic control in rats. |
title_fullStr |
Chronic treatment with ivabradine does not affect cardiovascular autonomic control in rats. |
title_full_unstemmed |
Chronic treatment with ivabradine does not affect cardiovascular autonomic control in rats. |
title_sort |
Chronic treatment with ivabradine does not affect cardiovascular autonomic control in rats. |
author |
Silva, Fernanda Cacilda dos Santos |
author_facet |
Silva, Fernanda Cacilda dos Santos Paiva, Franciny Aparecida Ribeiro, Flavia Camargos de Figueiredo Müller Caldeira, Henrique Martins Arantes Fontes, Marco Antônio Peliky Menezes, Rodrigo Cunha Alvim de Casali, Karina Rabello Fortes, Gláucia Helena Tobaldini, Eleonora Solbiati, Monica Montano, Nicola Silva, Valdo José Dias da Chianca Júnior, Deoclécio Alves |
author_role |
author |
author2 |
Paiva, Franciny Aparecida Ribeiro, Flavia Camargos de Figueiredo Müller Caldeira, Henrique Martins Arantes Fontes, Marco Antônio Peliky Menezes, Rodrigo Cunha Alvim de Casali, Karina Rabello Fortes, Gláucia Helena Tobaldini, Eleonora Solbiati, Monica Montano, Nicola Silva, Valdo José Dias da Chianca Júnior, Deoclécio Alves |
author2_role |
author author author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Silva, Fernanda Cacilda dos Santos Paiva, Franciny Aparecida Ribeiro, Flavia Camargos de Figueiredo Müller Caldeira, Henrique Martins Arantes Fontes, Marco Antônio Peliky Menezes, Rodrigo Cunha Alvim de Casali, Karina Rabello Fortes, Gláucia Helena Tobaldini, Eleonora Solbiati, Monica Montano, Nicola Silva, Valdo José Dias da Chianca Júnior, Deoclécio Alves |
dc.subject.por.fl_str_mv |
Renal sympathetic nerve activity Cardiovascular reflexes Tonic control Vagal Activity |
topic |
Renal sympathetic nerve activity Cardiovascular reflexes Tonic control Vagal Activity |
description |
A low resting heart rate (HR) would be of great benefit in cardiovascular diseases. Ivabradine-a novel selective inhibitor of hyperpolarization-activated cyclic nucleotide gated (HCN) channels- has emerged as a promising HR lowering drug. Its effects on the autonomic HR control are little known. This study assessed the effects of chronic treatment with ivabradine on the modulatory, reflex and tonic cardiovascular autonomic control and on the renal sympathetic nerve activity (RSNA). Male Wistar rats were divided in 2 groups, receiving intraperitoneal injections of vehicle (VEH) or ivabradine (IVA) during 7 or 8 consecutive days. Rats were submitted to vessels cannulation to perform arterial blood pressure (AP) and HR recordings in freely moving rats. Time series of resting pulse interval and systolic AP were used to measure cardiovascular variability parameters. We also assessed the baroreflex, chemoreflex and the Bezold-Jarish reflex sensitivities. To better evaluate the effects of ivabradine on the autonomic control of the heart, we performed sympathetic and vagal autonomic blockade. As expected, ivabradine-treated rats showed a lower resting (VEH: 362 ± 16 bpm vs. IVA: 260 ± 14 bpm, p = 0.0005) and intrinsic HR (VEH: 369 ± 9 bpm vs. IVA: 326 ± 11 bpm, p = 0.0146). However, the chronic treatment with ivabradine did not change normalized HR spectral parameters LF (nu) (VEH: 24.2 ± 4.6 vs. IVA: 29.8 ± 6.4; p > 0.05); HF (nu) (VEH: 75.1 ± 3.7 vs. IVA: 69.2 ± 5.8; p > 0.05), any cardiovascular reflexes, neither the tonic autonomic control of the HR (tonic sympathovagal index; VEH: 0.91± 0.02 vs. IVA: 0.88 ± 0.03, p = 0.3494). We performed the AP, HR and RSNA recordings in urethane-anesthetized rats. The chronic treatment with ivabradine reduced the resting HR (VEH: 364 ± 12 bpm vs. IVA: 207 ± 11 bpm, p < 0.0001), without affecting RSNA (VEH: 117 ± 16 vs. IVA: 120 ± 9 spikes/s, p = 0.9100) and mean arterial pressure (VEH: 70 ± 4 vs. IVA: 77 ± 6 mmHg, p = 0.3293). Our results suggest that, in health rats, the long-term treatment with ivabradine directly reduces the HR without changing the RSNA modulation and the reflex and tonic autonomic control of the heart. |
publishDate |
2016 |
dc.date.issued.fl_str_mv |
2016 |
dc.date.accessioned.fl_str_mv |
2018-02-15T12:04:22Z |
dc.date.available.fl_str_mv |
2018-02-15T12:04:22Z |
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info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
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article |
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publishedVersion |
dc.identifier.citation.fl_str_mv |
SILVA, F. C. dos et al. Chronic treatment with ivabradine does not affect cardiovascular autonomic control in rats. Frontiers in Physiology, v. 7, p. 1-10, 2016. Disponível em: <http://journal.frontiersin.org/article/10.3389/fphys.2016.00305/full>. Acesso em: 15 set. 2017. |
dc.identifier.uri.fl_str_mv |
http://www.repositorio.ufop.br/handle/123456789/9531 |
dc.identifier.issn.none.fl_str_mv |
1664-042X |
dc.identifier.doi.none.fl_str_mv |
https://doi.org/10.3389/fphys.2016.00305 |
identifier_str_mv |
SILVA, F. C. dos et al. Chronic treatment with ivabradine does not affect cardiovascular autonomic control in rats. Frontiers in Physiology, v. 7, p. 1-10, 2016. Disponível em: <http://journal.frontiersin.org/article/10.3389/fphys.2016.00305/full>. Acesso em: 15 set. 2017. 1664-042X |
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http://www.repositorio.ufop.br/handle/123456789/9531 https://doi.org/10.3389/fphys.2016.00305 |
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eng |
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