title: Possible mechanisms for brain natriuretic peptide resistance in heart failure with a focus on interspecies differences and canine BNP biology.
abstract: B-type natriuretic peptide or brain natriuretic peptide (BNP) is a cardiac peptide hormone. The principal stimulus for BNP synthesis is myocyte stretch. BNP binds to the natriuretic peptide receptor-A causing increased intracellular cyclic guanosine monophosphate (cGMP) production and shows cardio- and renoprotective effects. However, high endogenous BNP levels are associated with a lack of effect in severe heart failure. Moreover, in experimental heart failure, the response to treatments targeting the natriuretic peptide system is attenuated. This article reviews potential mechanisms that may explain the 'BNP paradox' in heart failure with a focus on interspecies differences, on known and presumed specificities of canine BNP biology, and on experimental studies in dogs. Resistance to BNP is far from fully understood but may be due to post-translational modifications and alteration in proBNP processing, receptor downregulation and desensitization, blunted intracellular signalling and increased clearance of BNP(1-32.) Alternatively, resistance to BNP may be due to BNP(1-32) shortening into additional truncated forms that are less biologically effective. Future improvement in understanding of BNP biology may provide the rationale for innovative therapeutic strategies to maximize cardiovascular and renal cGMP bioavailability.
authors.affiliation: Laboratory of Medical Biochemistry, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, UA, Antwerp, Belgium.
authors.forename: Lesley
authors.initials: L
authors.lastname: Baerts
authors.forename: Nelson
authors.initials: N
authors.lastname: Gomez
authors.forename: Marc
authors.initials: M
authors.lastname: Vanderheyden
authors.forename: Ingrid
authors.initials: I
authors.lastname: De Meester
authors.forename: Kathleen
authors.initials: K
authors.lastname: Mc Entee
mesh_terms: D000818:Animals; D004283:Dog Diseases / Q000378:metabolism*; D004285:Dogs; D006333:Heart Failure / Q000378:metabolism / Q000662:veterinary*; D020097:Natriuretic Peptide, Brain / Q000378:metabolism*; D013045:Species Specificity
chemical_list: D020097:Natriuretic Peptide, Brain