Although brain natriuretic peptide (BNP) was originally isolated from porcine brain, it was subsequently found to be more abundant in cardiac ventricles. Of all the natriuretic peptides, the amino-acid sequence of BNP varies most among species. For instance, in human, pig, and rat, mature BNP is 32, 26, and 45 amino acids in length, respectively.
Human BNP cDNA encodes a 132 amino-acid preprohormone that is processed to a 105-residue prohormone by removal of the signal peptide. Both corin and the endopeptidase, furin, have been shown to cleave the prohormone into the 32 amino-acid mature peptide. In the myocyte, BNP mRNA levels are regulated transcriptionally and posttranscriptionally in response to increased ventricular filling pressures or mechanical stretch. BNP is functionally similar to ANP
with respect to its vasorelaxant, natriuretic, and diuretic properties, but normal plasma BNP levels are only one-seventeenth of ANP levels. In contrast to ANP, ventricular BNP is not stored in secretory granules, instead it is released in a constitutive fashion following synthesis. Transgenic mice overexpressing BNP exhibited reduced blood pressure and cardiac weight accompanied by an elevation of plasma cGMP concentrations. They also exhibit increased long bone growth that most likely results from cross-activation of NPR-B. BNP null mice have normal blood pressures, but display pressure-sensitive cardiac fibrosis, proliferation of interstitial fibroblasts, and elevated ventricular extracellular matrix proteins. Hence, BNP's main function may be to regulate the cardiac ventricles.
BNP release is directly proportional to ventricular volume expansion and pressure overload. Although ANP is elevated in patients with congestive heart failure, BNP levels correlate more closely with left ventricular pressure, amount of dyspnea, and the state of neurohormonal modulation. Therefore, BNP, more than ANP, is an excellent indicator of heart failure. A rapid, whole-blood BNP assay (Triage BNP Test, Biosite Inc., San Diego, CA) that allows quick evaluation of patient plasma BNP levels was recently approved by the US Food and Drug Administration. Normal human plasma levels of BNP are <40 pg ml"1 and levels greater than 100 pg ml"1 are highly correlated with congestive heart failure. The high negative predictive value of this measurement suggests that it may be extremely useful in ruling out cardiac abnormalities in patients with dyspnea.
Recombinant B-type natriuretic peptide, whose clinical and trade names are Nesiritide and Natrecor, respectively, mimics the actions of endogenous BNP. It has been studied in more than 1700 patients with acute decompensated heart failure and has been shown to cause potent, dose-related vasodilation that is rapid in onset and sustained for the duration of drug infusion. It was approved for the treatment of acute decompensated congestive heart failure by the Food and Drug Administration in 2001.
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