Impaired natriuretic and renal endocrine response to acute volume expansion in pre-clinical systolic and diastolic dysfunction

Paul M. McKie, John A. Schirger, Lisa C. Costello-Boerrigter, Sherry L. Benike, Lynn K. Harstad, Kent R. Bailey, David O. Hodge, Margaret M. Redfield, Robert D. Simari, John C. Burnett, Horng H. Chen

Research output: Contribution to journalArticlepeer-review

51 Scopus citations


Objectives: 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.

Original languageEnglish (US)
Pages (from-to)2095-2103
Number of pages9
JournalJournal of the American College of Cardiology
Issue number20
StatePublished - Nov 8 2011


  • B-type natriuretic peptide
  • cyclic guanosine monophosphate
  • diastolic dysfunction
  • heart failure
  • natriuretic peptide
  • pre-clinical
  • systolic dysfunction

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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