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Atrial natriuretic peptide and urinary cyclic guanosine monophosphate in patients with chronic heart failure
W T Abraham1, J Hensen, J K Kim
1Department of Medicine, University of Colorado School of Medicine, Denver 80262.
Insights
In heart failure patients, elevated human atrial natriuretic peptide (hANP) correlates with increased urinary cyclic guanosine monophosphate (cGMP), indicating a blunted natriuretic effect despite higher peptide levels.
Area of Science:
- Cardiology
- Endocrinology
- Nephrology
Background:
- Circulating human atrial natriuretic peptide (hANP) is elevated in heart failure.
- The natriuretic effect of hANP is diminished in heart failure patients.
- Urinary cyclic guanosine monophosphate (cGMP) is a key intracellular mediator of hANP's natriuretic actions.
Purpose of the Study:
- To investigate the relationship between endogenous hANP and urinary cGMP in patients with heart failure.
- To explore the correlation between central hemodynamics and these biomarkers in heart failure.
Main Methods:
- Studied six patients with heart failure (NYHA Classes II-IV, no medications) and four normal subjects.
- Measured supine plasma hANP and urinary cGMP concentrations.
- Performed right heart catheterization to assess central hemodynamics in heart failure patients.
Main Results:
- Heart failure patients exhibited significantly higher plasma hANP (139.0 ± 42.0 pg/mL vs. 22.0 ± 6.1 pg/mL) and urinary cGMP excretion rates (1.14 ± 0.31 nmol/min vs. 0.35 ± 0.05 nmol/min) compared to controls (P < 0.05).
- In heart failure patients, right atrial pressure positively correlated with plasma hANP (r = 0.96) and urinary cGMP (r = 0.93).
- Plasma hANP strongly correlated with urinary cGMP concentration (r = 0.91) in heart failure patients.
Conclusions:
- Despite elevated hANP levels in heart failure, the correlation with urinary cGMP suggests a blunted biological response.
- Hemodynamic status, indicated by right atrial pressure, is closely linked to both hANP and cGMP levels in heart failure.
Abstract:
Circulating concentrations of human atrial natriuretic peptide (hANP) are elevated in patients with heart failure; however, the natriuretic effect of hANP is blunted in these patients. In this study, the relationship between urinary cGMP, the second messenger for the natriuretic effect of hANP in vivo, and endogenous hANP was examined in six patients with heart failure and four normal subjects. In addition, right heart catheterization for the determination of central hemodynamics was performed in the heart failure patients. The heart failure patients were in New York Heart Association Classes II to IV and were receiving no medications at the time of the study. Supine plasma hANP and urinary cGMP concentrations were determined on two occasions in each subject, as were right and left atrial pressures in the heart failure patients. At the time of study, the patients were in positive sodium balance, and control subjects were in normal sodium balance. Plasma hANP and urinary cGMP excretion rates were elevated in heart failure patients as compared with those in controls: hANP, 139.0 +/- 42.0 versus 22.0 +/- 6.1 pg/mL (P less than 0.05); urinary cGMP, 1.14 +/- 0.31 versus 0.35 +/- 0.05 nmol/min (P less than 0.05). In heart failure patients, right atrial pressure correlated positively with plasma hANP (r = 0.96; P less than 0.01) and urinary cGMP concentrations (r = 0.93; P less than 0.05) and the excretion rate (r = 0.92; P less than 0.05). Moreover, plasma hANP was strongly correlated with urinary cGMP concentration (r = 0.91; P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)