Myocardial Natriuretic Peptides and Oxygen Metabolism in Heart Failure

Since the discovery of natriuretic peptides in the 1980s, initially as A-type natriuretic peptide, followed by B-type natriuretic peptide, their measurement has become standard in the management of heart failure (HF), as levels are markedly elevated in patients with HF. However, systematic reviews conducted in this area have yielded inconclusive results. Position and consensus papers on natriuretic peptides and HF have uniformly adopted the paradigm that myocardial stretch is the underlying mechanism explaining elevated circulating natriuretic peptide levels. Although mechanical stress is the primary factor determining myocardial oxygen consumption, this relationship has not been studied in HF. Biological evolution has developed a specific hypoxia-sensitive pathway in which a nuclear transcription factor, hypoxia-inducible factor, serves as the oxygen sensor, enabling myocardial cells to respond to reduced oxygen tension. In myocardial cell cultures, hypoxia was found to be a direct and sufficient stimulus for the expression of natriuretic peptides via the hypoxia-inducible factor pathway. Myocardial oxygen metabolism, which regulates plasma natriuretic peptide levels, presents a new objective for clinical research in HF.