Clinical implications of defective B-type natriuretic peptide.
Our understanding of the natriuretic peptide system continues to evolve rapidly. B-type natriuretic peptide (BNP), originally thought to be a simple volume-regulating hormone that is produced in response to cardiac stretch, has been shown to also play important roles in modulating bronchodilation, endothelial function, and cardiac remodeling. Recent data demonstrate that elevated levels of BNP in patients with heart failure do not represent a simple ratcheting up of normal production in response to increased stimulus. Instead, we now know that chronic stimulation of BNP synthesis induces a reversion to fetal gene expression, resulting in production of high molecular weight forms of BNP that are functionally deficient. Standard point-of-care BNP assays are immunoassays that will detect any molecule containing the target epitopes. Consequently, these assays cannot distinguish between defective, high molecular weight forms of BNP and normal, physiologically active BNP. In 2 separate evaluations, mass spectroscopy detected little, if any, normal BNP in patients with heart failure, despite the appearance of high circulating levels of immunoreactive BNP (iBNP) using commercial assays. Therefore, these commercial assays should be considered to be only an indication of myocardial stress. They do not measure physiologic BNP activity. This accounts for the "BNP paradox," namely, that administration of exogenous recombinant human BNP (rhBNP, nesiritide) has substantial clinical and hemodynamic impact in the presence of high levels of circulating iBNP using commercial assays. In addition to its short-term hemodynamic impact, rhBNP may have other important effects in this setting, and further investigation is warranted.
Menon
Santosh G
SG
The Ohio Heart & Vascular Center, Cincinnati, Ohio 45242, USA. menons@ohioheart.org
Mills
Roger M
RM
Schellenberger
Ute
U
Saqhir
Syed
S
Protter
Andrew A
AA
D009320:Atrial Natriuretic Factor / Q000097:blood / Q000502:physiology; D003404:Creatinine / Q000097:blood; D005355:Fibrosis; D006333:Heart Failure / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D006984:Hypertrophy; D007118:Immunoassay; D009206:Myocardium / Q000473:pathology; D045283:Natriuretic Agents / Q000627:therapeutic use*; D020097:Natriuretic Peptide, Brain / Q000097:blood / Q000502:physiology* / Q000627:therapeutic use*; D012084:Renin-Angiotensin System / Q000502:physiology
D045283:Natriuretic Agents; D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor; D003404:Creatinine