title: Impaired natriuretic and renal endocrine response to acute volume expansion in pre-clinical systolic and diastolic dysfunction.
abstract: OBJECTIVE
  We hypothesized an impaired renal endocrine and natriuretic response to volume expansion (VE) in humans with pre-clinical systolic dysfunction (PSD) and pre-clinical diastolic dysfunction (PDD). We further hypothesized that exogenous B-type natriuretic peptide (BNP) could rescue an impaired natriuretic response in PSD and PDD.
  
  
  BACKGROUND
  Recent reports suggest that in early systolic heart failure (HF), there is an impaired natriuretic response to acute VE.
  
  
  METHODS
  PSD was defined as left ventricular ejection fraction <40% without HF symptoms. PDD was defined as ejection fraction >50%, moderate to severe diastolic dysfunction by Doppler criteria, and no HF symptoms. A double-blinded, placebo-controlled, crossover study was employed to determine the renal response to VE (0.25 ml/kg/min of normal saline for 60 min) in the presence and absence of exogenous BNP. Twenty healthy control subjects, 20 PSD subjects, and 18 PDD subjects participated.
  
  
  RESULTS
  In healthy control subjects, urinary cyclic guanosine monophosphate (cGMP) and natriuresis increased after VE. In contrast, among PSD and PDD subjects, there was a paradoxical decrease in urinary cGMP and attenuated natriuresis. Pre-treatment with subcutaneous BNP resulted in similar increases in both urinary cGMP and natriuresis among healthy normal, PSD, and PDD subjects.
  
  
  CONCLUSIONS
  In PSD and PDD, there is impaired renal cGMP activation, which contributes to impaired natriuresis in response to VE. Impaired activation of urinary cGMP and reduced natriuresis may contribute to volume overload and the progression of HF among PSD and PDD subjects. Importantly, the impaired renal excretory response to VE is rescued by exogenous BNP in PSD and PDD.
authors: Cardiorenal Research Laboratory, Division of Cardiovascular Diseases, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA.
authors: Paul M
authors: PM
authors: McKie
authors: John A
authors: JA
authors: Schirger
authors: Lisa C
authors: LC
authors: Costello-Boerrigter
authors: Sherry L
authors: SL
authors: Benike
authors: Lynn K
authors: LK
authors: Harstad
authors: Kent R
authors: KR
authors: Bailey
authors: David O
authors: DO
authors: Hodge
authors: Margaret M
authors: MM
authors: Redfield
authors: Robert D
authors: RD
authors: Simari
authors: John C
authors: JC
authors: Burnett
authors: Horng H
authors: HH
authors: Chen
mesh_terms: D000328:Adult; D000368:Aged; D001810:Blood Volume / Q000502:physiology*; D016022:Case-Control Studies; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006157:Guanosine Monophosphate / Q000652:urine; D054144:Heart Failure, Diastolic / Q000209:etiology* / Q000503:physiopathology / Q000652:urine; D054143:Heart Failure, Systolic / Q000209:etiology* / Q000503:physiopathology / Q000652:urine; D006801:Humans; D007668:Kidney / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009318:Natriuresis / Q000502:physiology*; D020097:Natriuretic Peptide, Brain; D012964:Sodium / Q000652:urine
chemical_list: D020097:Natriuretic Peptide, Brain; D006157:Guanosine Monophosphate; D012964:Sodium