An 8% high-salt diet in female Dahl salt-sensitive rats successfully established a HFpEF model, significantly elevating systolic blood pressure (237.0 vs 128.4 mmHg, p<0.05).
Does an 8% high-salt diet and subsequent acute sympathetic activation induce a HFpEF phenotype and acute exacerbation in female Dahl salt-sensitive rats?
This study successfully establishes a female hypertensive HFpEF rat model and demonstrates that acute sympathetic activation exacerbates left atrial pressure overload, highlighting a potential mechanism for acute HFpEF exacerbations in women.
Absolute Event Rate: 237% vs 128.4%
p-value: p=<0.05
Abstract Background Heart failure with preserved ejection fraction (HFpEF) is prevalent in women and common in patients with hypertension. However, a female hypertensive HFpEF animal model has not been established. Furthermore, sympathetic activation is suggested to play a crucial role in HFpEF pathophysiology, but its contribution, particularly in women, remains unclear. Purpose To establish a female hypertensive HFpEF model and investigate whether sympathetic activation contributes to acute exacerbation of HFpEF. Methods and Results (1) Seven-week-old female Dahl salt-sensitive rats were subjected to an 8% high-salt diet (HS group, n=6) or a 0.3% low-salt diet (LS group, n=9, control). In the HS group, systolic blood pressure (237.0 ± 7.2 vs 128.4 ± 1.6 mmHg, p0.05) and heart rate (465 ± 9 vs 409 ± 7 bpm, p0.05) were significantly elevated (Fig. 1). Although left ventricular ejection fraction remained preserved on echocardiography, the HS group exhibited increased left ventricular wall thickness, a decreased E/A ratio, and an increased E/e’ ratio, indicating diastolic dysfunction. Furthermore, left ventricular end-diastolic pressure (12.4 ± 1.1 vs 5.4 ± 0.5 mmHg, p0.05), left ventricular weight, and lung weight were significantly increased. Histological and PCR analyses confirmed myocardial hypertrophy and fibrosis. In addition, plasma noradrenaline levels and neuronal activity in the rostral ventrolateral medulla were elevated, indicating that this model presents a HFpEF phenotype with increased sympathetic activation. (2) To assess the impact of acute sympathetic activation, we used this female HFpEF model to perform stress-loading experiments. A telemetry device for left atrial pressure measurement was implanted at 12 weeks, and at 13 weeks, conscious rats underwent 30-minute stress loading to induce acute sympathetic activation, during which hemodynamic parameters were assessed. Compared with the high-salt non-loaded group (n=5), the high-salt loaded group (n=5) exhibited a significant increase in left atrial pressure (7.2 ± 2.4 vs 3.9 ± 1.0 mmHg, p0.05) with elevated mean arterial pressure and heart rate following stress loading (Fig. 2). At the end of the experiment, plasma noradrenaline levels were significantly higher in the high-salt loaded group than in the high-salt non-loaded group. In contrast, in the low-salt group, the increase in left atrial pressure was less pronounced. Conclusion A female hypertensive HFpEF model was successfully established in Dahl salt-sensitive rats, characterized by left ventricular hypertrophy and fibrosis, as well as sympathetic overactivation. Using this model, we demonstrated that acute sympathetic activation in the pre-heart failure phase induced left atrial pressure overload, suggesting its contribution to HFpEF exacerbation.
Nakashima et al. (Sat,) conducted a other in Heart failure with preserved ejection fraction (HFpEF) (n=25). 8% high-salt diet vs. 0.3% low-salt diet was evaluated on Systolic blood pressure (p=<0.05). An 8% high-salt diet in female Dahl salt-sensitive rats successfully established a HFpEF model, significantly elevating systolic blood pressure (237.0 vs 128.4 mmHg, p<0.05).