We have recently identified a novel @entity1472 -terminal fragment of pro-brain natriuretic peptide (NT-proBNP) in the circulation of @entity1 , the concentration of which increases progressively as the left ventricle fails. To clarify the origins of NT-proBNP in experimental animals, we have developed an RIA for NT-proBNP based on residues 52-71 of ovine proBNP-(1-103) and used it to study cardiac processing, secretion, and metabolism of @entity70439 in @entity742 with @entity299 induced by coronary artery ligation (CAL) or rapid left ventricular pacing (rLVP). The concentration of NT-proBNP in left atrial plasma extracts drawn from normal control @entity742 was threefold that of mature @entity70439 . Size-exclusion and reverse-phase HPLC analyses of plasma extracts coupled to RIA revealed a single peak of immunoreactive (ir) NT-proBNP [ approximately 8,000 relative molecular weight (Mr)], quite distinct from a single peak of ir-mature @entity70439 ( approximately 3,000 Mr). In contrast, ovine cardiac tissue contained only a single immunoreactive peak of high-molecular-weight @entity70439 ( approximately 11,000 Mr), consistent in size with proBNP-(1-103). Sampling from the cardiac coronary sinus in normal control @entity742 (n = 5) and @entity742 with CAL (n = 5) revealed that the molar ratio of NT-proBNP to mature @entity70439 was similar. There was a significant gradient of both mature and NT-proBNP across the heart in normal @entity742 , whereas after CAL the gradient was significant for mature @entity70439 only. In both forms of @entity299 (CAL and rLVP), left atrial plasma levels of NT-proBNP were significantly increased above normal levels, in contrast with mature @entity70439 levels, which were raised only in the rLVP group of animals. Blockade of natriuretic peptide metabolism in @entity742 with @entity712 (induced by rLVP) raised mature @entity70439 levels threefold but did not affect levels of NT-proBNP. In conclusion, these studies show that NT-proBNP is formed from proBNP stores during secretion and, compared with mature @entity70439 , accumulates in plasma because metabolism of NT-proBNP appears to differ from that of mature @entity70439 . Although its function, if any, remains unclear, plasma NT-proBNP may prove to be a sensitive marker of @entity299 .

@entity1472 -terminal proBNP in ovine plasma: evidence for enhanced secretion in response to XXXX .

@entity1 :: ('9606', 'Species') :: ['humans'] @entity70439 :: ('100294642(Tax:9940)', 'Gene') :: ['BNP'] @entity1472 :: ('CHEBI:46882', 'Chemical') :: ['amino'] @entity712 :: ('MESH:D006333', 'Disease') :: ['heart failure'] @entity742 :: ('9940', 'Species') :: ['sheep'] @entity299 :: ('MESH:D006331', 'Disease') :: ['cardiac overload', 'cardiac overload and/or decompensation']
@entity299 :: (MESH:D006331,Disease) :: ['cardiac overload']
