Exercise Training Does Not Alter Nitric Oxide Metabolites in Heart Failure

Overview

This study analyzed the impact of high-intensity interval training (HIIT) and moderate continuous training (MCT) on nitric oxide (NO) metabolites in patients with heart failure with reduced (HFrEF) and preserved ejection fraction (HFpEF). Despite baseline differences in NO metabolite profiles linked to heart failure severity, neither exercise modality significantly changed plasma NO metabolite levels at 3 or 12 months.

Background

Endothelial dysfunction is a key factor in cardiovascular diseases including heart failure, affecting exercise capacity and vascular health. Nitric oxide (NO) plays a central role in endothelial function, with metabolites such as L-arginine and homoarginine promoting NO bioavailability, while ADMA and SDMA inhibit it. Exercise training improves exercise capacity and endothelial function in heart failure, particularly in HFrEF, but its effect on NO metabolites remains unclear. This study investigates whether supervised HIIT or MCT influences systemic NO metabolite concentrations in HFrEF and HFpEF patients.

Data Highlights

NO metabolites correlated significantly with exercise capacity (VO2peak) and NT-proBNP but not with endothelial function measures (reactive hyperaemia index, flow-mediated dilation). No significant changes in NO metabolites were observed after 3 months of HIIT or MCT or at 12-month follow-up in either HF group.

Key Findings

• Baseline homoarginine and ADMA levels were significantly higher in HFrEF compared to HFpEF patients.
• NO metabolite profiles correlated with heart failure severity markers such as VO2peak and NT-proBNP.
• No significant association was found between NO metabolites and clinical measures of endothelial function.
• Microvascular endothelial dysfunction was more frequent in HFrEF than HFpEF, contrary to initial expectations.
• Neither HIIT nor MCT significantly altered plasma concentrations of L-arginine, homoarginine, ADMA, or SDMA at 3 or 12 months.

Clinical Implications

Although exercise training improves exercise capacity in heart failure, it does not appear to modify circulating NO metabolite levels, suggesting that improvements in endothelial function may occur through mechanisms independent of systemic NO metabolite changes. Clinicians should consider that HIIT and MCT do not differentially impact NO bioavailability markers in HFrEF or HFpEF, and other therapeutic strategies may be needed to target endothelial dysfunction at the metabolic level.

Conclusion

This study demonstrates that supervised exercise training, whether high-intensity interval or moderate continuous, does not significantly influence systemic nitric oxide metabolite concentrations in patients with heart failure, despite baseline associations with disease severity. These findings highlight the complexity of endothelial dysfunction in heart failure and the need for further research into targeted metabolic interventions.

References

1. SMARTEX-HF and OptimEx-Clin Trials -- Impact of Exercise Training on Nitric Oxide Metabolites in Heart Failure
2. Bahls M, Kränkel N, 2023 -- A whisper from the endothelium: can we hear it?