Abstract

Introduction: Hypertension is a major risk factor for the development of heart failure with preserved ejection fraction (HFpEF). A high-salt diet has shown to induce hypertension and HFpEF in Dahl salt-sensitive rats; however, once developed, it is unclear if HFpEF resolves after a return to low-salt diet. Hypothesis: Dietary modification to reduce salt content will decrease blood pressure and lead to resolution of HFpEF in Dahl salt-sensitive rats. Methods: Dahl salt-sensitive rats (n=12) were fed a high-salt (HS) diet (8% NaCl) from 7 weeks of age to induce HFpEF. Rats fed a normal-salt (NS) diet (0.3% NaCl; n=6) served as controls. The development of HFpEF was verified with an echocardiogram at 14 weeks of age in HS-fed rats. HS diet was then switched to NS diet in a subset of the HFpEF rats (HFpEF s/p NS, n=6) at 16 weeks of age, while the rest of the HFpEF rats continued to consume HS diet (HFpEF s/p HS, n=6). Blood pressure was measured non-invasively using a tail artery cuff. Echocardiography was performed to measure systolic and diastolic function. Programmed electrical stimulation was performed to induce ventricular arrhythmias. Results: In rats with HFpEF, a switch to NS diet improved diastolic function (E/E’ ratio 14.9±3.0 in HFpEF s/p NS vs. 25.3±8.2 in HFpEF s/p HS, p=0.045). However, the diet switch did not reduce systolic blood pressure (204±15 mmHg in HFpEF s/p HS vs. 194±21 mmHg in HFpEF s/p NS, p=0.44). Lung congestion was also significantly reduced after NS diet in rats with HFpEF (lung/body weight 0.39±0.03% in HFpEF s/p NS vs. 0.50±0.06% in HFpEF s/p HS, p=0.0040). Ventricular arrhythmia inducibility did not change after diet switch (100% in both HFpEF s/p HS and HFpEF s/p NS rats), nor did the duration of induced ventricular arrhythmias (75±3 beats in HFpEF s/p HS vs. 67±8 beats in HFpEF s/p NS, p=0.0749). QTc intervals did not decrease after diet changes in rats with HFpEF (226±29 ms in HFpEF s/p HS vs. 225±4 ms in HFpEF s/p NS, p=0.095). Conclusions: Diet modification improves diastolic function and reduces pulmonary congestion in Dahl salt-sensitive rats with HFpEF, but it did not reduce blood pressure or inducibility of ventricular arrhythmias. Further mechanistic study is warranted to further investigate the effects of diet on HFpEF progression.

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