Gene expression and secretion of the cardiac polypeptide hormones atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP) are simultaneously upregulated in various cardiac disorders such as congestive heart failure, ischemic heart disease, and hypertensive heart disease, in which hemodynamic or neuroendocrine changes are key components in the progression of disease. However, during acute cardiac allograft rejection, plasma BNP levels are increased but not those of ANF. Successful treatment of the rejection episode decreases the elevated plasma BNP to prerejection values suggesting that substances related to inflammation may selectively influence BNP gene expression. Indeed, cytokines such as TNFα and IL-1β selectively stimulate cardiac BNP at the transcriptional and translational levels in cardiomyocyte cultures without affecting ANF. This selective BNP increase is seen in vivo, in addition to acute cardiac allograft rejection, in several circumstances where inflammation significantly contributes to the pathogenesis of disease such as in sepsis and in acute myocarditis. 1. Introduction Seven years after the discovery of the natriuretic factor from the atria of the heart (ANF) [1, 2] and five years after the first purification and sequencing of its circulating form [3], brain natriuretic peptide (BNP) was isolated from porcine brain [4]. Subsequently, BNP was found to be most abundantly expressed in the atria of the heart. The biologically active, circulating forms of these cardiac natriuretic peptides (NPs) ANF ( ) and BNP ( ) are C-terminal fragments from their respective prohormones: and . The N-terminal fragments of ANF (NT-proANF) and BNP (NT-proBNP) coexist in blood with the C-terminal fragments. Measurement of both N- and C-terminal peptides in blood has been used in clinical studies in relation to cardiovascular disorders [5]. ANF and BNP share most biological properties including diuretic, natriuretic, vasorelaxant, and cardiac antihypertrophic and antifibrotic properties that are effected by signaling through a common receptor: the guanylyl cyclase- (GC-) A receptor [6]. However, some differences between ANF and BNP have been reported on control of gene expression and phenotype arising from observations in transgenic animals. BNP gene expression was induced more rapidly than that of ANF in the left ventricles following coronary artery ligation in rats [7]. Mice with genetically reduced production of ANF can lead to salt-sensitive hypertension [8], but mice with targeted disruption of the BNP gene develop multifocal fibrotic lesions
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