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Title: Chronic treatment with ivabradine does not affect cardiovascular autonomic control in rats.
Authors: 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
Keywords: Renal sympathetic nerve activity
Cardiovascular reflexes
Tonic control
Vagal Activity
Issue Date: 2016
Citation: 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: <>. Acesso em: 15 set. 2017.
Abstract: 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.
ISSN: 1664-042X
metadata.dc.rights.license: 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 <>. Acesso em: 27 fev. 2020.
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