Oral brain natriuretic peptide: a novel strategy for chronic protein therapy for cardiovascular disease

In 1956, secretory granules were detected via electron microscopy in the mammalian atria by Kisch. This remarkable discovery signaled the beginning of a new field of research that decades later has lead to the concept of the heart as an endocrine organ and the establishment of the natriuretic peptide (NP) system. In 1981, deBold and colleagues identified from the atrial myocardium the first member of the NP family, atrial NP. Thereafter, new members of this growing family of cardiac hormones were identified and investigated. The successful story of B-type or brain NP (BNP), from its discovery to its use in the diagnosis and prognosis of cardiovascular diseases and later as a tool in the treatment of acute congestive heart failure, have since taken place. However, the use of peptides as chronic therapies has been limited by enzymatic degradation. Chronic administration of BNP, particularly in disease states like hypertension and early heart failure, could be effective as an antihypertensive therapy and in delaying progression of cardiac disease. To date, the use of BNP is limited to patients with acute decompensated heart failure, but new strategies are under investigation to extend the use of chronic BNP in less severe stages of cardiovascular diseases. Innovative technologies have been recently developed that allow protection of proteins from enzymatic degradation, making feasible oral administration of small proteins such as BNP. This review will focus on the potential role of BNP as a new chronic therapeutic strategy in the treatment of cardiovascular diseases and will summarize our recent report of the development and in vivo evaluation of orally active human BNP.