Abstract 15723: Vagus Nerve Stimulation Reduces Mean Arterial Pressure Through Structural and Electrical Remodeling of the Heart in Dahl Salt-Sensitive Rat Hypertension Model
Hypertension (HTN) is one of the strongest risk factors for cardiovascular diseases, which leads to ventricular hypertrophy, systolic and diastolic dysfunctions. There is a clear need for novel and effective techniques to treat HTN and HTN-induced heart diseases, which are closely linked to autonomic nervous system imbalance. Here, we aimed to evaluate the use of intermittent vagal nerve stimulation (VNS) as a novel therapy for the treatment of HTN.
HTN was induced in 6 Dahl salt-sensitive rats after 6 weeks of high salt diet (8% NaCl). Rats were implanted with the pressure monitoring transmitters and either active (VNS, n=3) or non-functional (Sham, n=3) VNS stimulators. Intermittent VNS was activated at week 7, and mean arterial pressure (MAP) was monitored for 4 more weeks. Optical mapping was performed in isolated rat hearts, and action potential durations (APD), intra-ventricular heterogeneity of APD (μ) and conduction velocity (CV) were measured at different pacing cycle lengths (CL) both in right (RV) and left ventricles (LV) (data are shown for CL = 200 ms).
HTN was successfully induced in rats as the MAP was significantly increased from week 1 to week 6 (107 ± 0.8 vs 171 ± 9.2 mmHg, p<0.05). During the first 2 weeks of VNS, MAP was increased in both Sham (194 ± 10.5 mmHg) and VNS rats (189 ± 18.3 mmHg), but no significant difference between the groups was observed. Afterwards, during the next 2 weeks of VNS, MAP continued to increase in Sham (210 ± 15.5 mmHg), but not in VNS rats (187 ± 24.4 mmHg, p<0.05 with Sham), indicating a therapeutic effect of VNS.
The tibial length normalized to heart weight ratio was reduced in VNS (0.33 ± 0.02 g/cm) in comparison to Sham rats (0.40 ± 0.01 g/cm, p<0.05), indicating possible beneficial structural remodeling of the HTN-induced hypertrophy.
Optical mapping showed that, in VNS rats, APD was larger in LV (75 ± 1.1 ms) in comparison to RV (66 ± 2.5 ms, p<0.05), while no difference was found in Sham. In both ventricles, VNS decreased μ (RV: 0.31 ± 0.05 vs 0.50 ± 0.13 and LV: 0.15 ± 0.01 vs 0.39 ± 0.10, p<0.05), and increased CV (RV: 0.90 ± 0.07 vs 0.70 ± 0.02 m/s and LV: 0.89 ± 0.05 vs 0.74 ± 0.01 m/s, p<0.05).
Our data indicate that VNS reduces MAP in hypertensive rats and results in beneficial structural and electrical remodeling effects of the heart.
Author Disclosures: X. Xie: None. S.W. Lee: None. T. Senjem: None. K. Caron: None. J. Osborn: None. E.G. Tolkacheva: None.
- © 2014 by American Heart Association, Inc.