title: Subcutaneous administration of brain natriuretic peptide in experimental heart failure.
abstract: OBJECTIVE
  The objective of this investigation was to define for the first time the cardiorenal and humoral actions of repeated short-term administration of subcutaneous (SQ) brain natriuretic peptide (BNP) administration during the evolution of experimental heart failure.
  
  
  BACKGROUND
  The rationale of this study was based on BNP as a vasodilating, natriuretic, renin-inhibiting and lusitropic peptide of cardiac origin.
  
  
  METHODS
  First, we defined the cardiorenal and humoral responses to acute low and high dose (5 microg/kg or 25 microg/kg) of SQBNP in experimental heart failure to establish the acute efficacy of an SQ delivery. Second, we characterized the response to 10 days of repeated short-term administration of BNP during the evolution of experimental heart failure produced by rapid ventricular pacing.
  
  
  RESULTS
  Plasma BNP and 3',5'-cyclic guanosine monophosphate rapidly increased and peaked at 30 min after acute SQBNP administration with increases in urinary sodium excretion, urine flow and renal blood flow in association with reductions in cardiac filling pressures. After 10 days of repeated short-term administration of SQBNP, cardiac output was increased and systemic vascular resistance and pulmonary capillary wedge pressure were decreased, as compared with untreated dogs with heart failure.
  
  
  CONCLUSIONS
  This study demonstrated for the first time that repeated short-term administration of SQ BNP administration for 10 days during the evolution of left ventricular dysfunction in a canine model results in an improvement in cardiovascular hemodynamics. This investigation supports a potential novel strategy for the chronic administration of BNP in the therapeutics of heart failure.
authors.affiliation: Department of Physiology, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA. chen.horng@mayo.edu
authors.forename: H H
authors.initials: HH
authors.lastname: Chen
authors.forename: J A
authors.initials: JA
authors.lastname: Grantham
authors.forename: J A
authors.initials: JA
authors.lastname: Schirger
authors.forename: M
authors.initials: M
authors.lastname: Jougasaki
authors.forename: M M
authors.initials: MM
authors.lastname: Redfield
authors.forename: J C
authors.initials: JC
authors.lastname: Burnett
mesh_terms: D000818:Animals; D004285:Dogs; D006333:Heart Failure / Q000188:drug therapy*; D007279:Injections, Subcutaneous; D008297:Male; D020097:Natriuretic Peptide, Brain / Q000008:administration & dosage*
chemical_list: D020097:Natriuretic Peptide, Brain