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Life Sci ; 346: 122636, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38614307

RESUMEN

Malnutrition results in autonomic imbalance and heart hypertrophy. Overexpression of hyperpolarization-activated cyclic nucleotide-gated channels (HCN) in the left ventricles (LV) is linked to hypertrophied hearts and abnormal myocardium automaticity. Given that ivabradine (IVA) has emerging pleiotropic effects, in addition to the widely known bradycardic response, this study evaluated if IVA treatment could repair the autonomic control and cardiac damages in malnourished rats. AIM: Assess the impact of IVA on tonic cardiovascular autonomic control and its relationship with hemodynamics regulation, LV inflammation, and HCN gene expression in post-weaning protein malnutrition condition. MAIN METHODS: After weaning, male rats were divided into control (CG; 22 % protein) and malnourished (MG; 6 % protein) groups. At 35 days, groups were subdivided into CG-PBS, CG-IVA, MG-PBS and MG-IVA (PBS 1 ml/kg or IVA 1 mg/kg) received during 8 days. We performed jugular vein cannulation and electrode implant for drug delivery and ECG registration to assess tonic cardiovascular autonomic control; femoral cannulation for blood pressure (BP) and heart rate (HR) assessment; and LV collection to evaluate ventricular remodeling and HCN gene expression investigation. KEY FINDINGS: Malnutrition induced BP and HR increases, sympathetic system dominance, and LV remodeling without affecting HCN gene expression. IVA reversed the cardiovascular autonomic imbalance; prevented hypertension and tachycardia; and inhibited the LV inflammatory process and fiber thickening caused by malnutrition. SIGNIFICANCE: Our findings suggest that ivabradine protects against malnutrition-mediated cardiovascular damage. Moreover, our results propose these effects were not attributed to HCN expression changes, but rather to IVA pleiotropic effects on autonomic control and inflammation.


Asunto(s)
Sistema Nervioso Autónomo , Frecuencia Cardíaca , Hipertensión , Ivabradina , Ratas Wistar , Taquicardia , Animales , Ivabradina/farmacología , Masculino , Ratas , Taquicardia/tratamiento farmacológico , Taquicardia/fisiopatología , Hipertensión/tratamiento farmacológico , Hipertensión/fisiopatología , Frecuencia Cardíaca/efectos de los fármacos , Sistema Nervioso Autónomo/efectos de los fármacos , Sistema Nervioso Autónomo/fisiopatología , Inflamación/metabolismo , Inflamación/tratamiento farmacológico , Destete , Presión Sanguínea/efectos de los fármacos , Canales Regulados por Nucleótidos Cíclicos Activados por Hiperpolarización/metabolismo , Desnutrición/tratamiento farmacológico , Desnutrición Proteico-Calórica/tratamiento farmacológico , Desnutrición Proteico-Calórica/fisiopatología , Desnutrición Proteico-Calórica/complicaciones , Ventrículos Cardíacos/efectos de los fármacos , Ventrículos Cardíacos/fisiopatología , Remodelación Ventricular/efectos de los fármacos
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