Abstract 12581: Impaired Atrial Natriuretic Peptide Activation and Natriuresis in Response to Acute Volume Overload in Preclinical Diastolic and Systolic Dysfunction
Background: Recent reports suggest there is a lack of activation of the natriuretic peptide system in early heart failure (HF).
Hypothesis: In the current study we test the hypothesis that subjects with preclinical systolic diastolic dysfunction (PSD) and preclinical diastolic dysfunction (PDD) have impaired atrial natriuretic peptide (ANP) release and natriuresis in response to intravascular acute volume loading (AVL). We further hypothesized that exogenous B-type natriuretic peptide (BNP), which is the most natriuretic of the natriuretic peptides, could rescue the lack of ANP activation and subsequent impaired natriuresis in PSD and PDD.
Methods: PSD was defined at LVEF < 45% without HF symptoms. PDD was defined as EF > 45% and moderate to severe diastolic dysfunction by Doppler criteria but without HF symptoms. A double blinded, placebo-controlled cross over study was employed to determine the renal response to AVL (0.25 ml/kg/min of normal saline for 60 minutes) in the presence and absence of exogenous BNP (subcutaneous 25 μg/kg bolus). 18 PDD, 20 PSD, and 20 healthy control subjects participated. *p<0.05
Results: In healthy controls, in response to AVL, plasma ANP levels were maintained, urinary cGMP (the second messenger molecule of ANP) was increased*, and natriuresis* increased. In contrast, among subjects with PSD and PDD there was a paradoxical decrease in plasma ANP (PSD -8±20*; PDD -35±104* pg/ml), decreased urinary cGMP (PSD -86±160*; PDD -107±157* pmol/min), and attenuated natriuresis. In response to AVL and concomitant subcutaneous BNP, PSD and PDD subjects responded similarly to healthy controls with similar increases in both urinary cGMP* and natriuresis*.
Conclusions: In PSD and PDD there is impaired ANP release and renal cGMP activation resulting in impaired natriuresis in response to AVL. This suggests impairment of the cardiorenal endocrine response, specifically the natriuretic peptide system, in PSD and PDD. Impaired activation of the natriuretic peptide system and reduced natriuresis may contribute to the progression of HF in subjects with PSD and PDD. Importantly, the impaired renal excretory response to AVL is rescued by exogenous BNP in PSD and PDD.
- © 2010 by American Heart Association, Inc.