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Congestive heart failure: increased cardiac and extracardiac atrial natriuretic peptide gene expression
J E Poulos1, W R Gower, J T Sullebarger
1Department of Biochemistry, James A. Haley Veterans Hospital, Tampa, FL 33612, USA.
Insights
Atrial natriuretic peptide (ANP) gene expression and its prohormone increase in the stomach and heart ventricles of rats with congestive heart failure (CHF). This suggests a potential role for extracardiac ANP in CHF, warranting further investigation.
Area of Science:
- Cardiovascular Physiology
- Molecular Biology
- Gastroenterology
Background:
- Congestive heart failure (CHF) is a complex syndrome characterized by cardiac dysfunction.
- Atrial natriuretic peptide (ANP) is a hormone primarily produced by the heart, involved in regulating fluid balance and blood pressure.
- The role of ANP in extracardiac tissues during CHF is not well understood.
Purpose of the Study:
- To investigate whether atrial natriuretic peptide (ANP) gene expression increases in extracardiac tissues, in addition to the heart, during congestive heart failure (CHF).
- To characterize the product of ANP gene expression in these tissues and assess ANP metabolism in CHF.
Main Methods:
- Congestive heart failure (CHF) was induced in Sprague-Dawley rats via an aortocaval fistula, creating cardiac hypertrophy.
- ANP messenger RNA (mRNA) levels were quantified using RNAase protection analysis in various tissues, including atria, ventricles, liver, colon, and stomach.
- The ANP gene product was identified using high-performance gel permeation chromatography, and circulating ANP concentrations and urinary excretion were measured.
Main Results:
- ANP steady-state mRNA levels significantly increased in the stomach antrum (4.2-fold) and heart ventricles (4.3-fold) of CHF rats compared to controls.
- ANP gene expression was detected but not elevated in the atria, liver, and other gastrointestinal tract sections.
- The product of ANP gene expression in both the stomach and heart ventricles of CHF animals was identified as the ANP prohormone, with no evidence of decreased renal metabolism.
Conclusions:
- ANP gene expression, specifically its steady-state mRNA, is upregulated in extracardiac tissue (stomach antrum) and the heart ventricle in the context of CHF.
- The ANP prohormone is the common product of ANP gene expression in both the heart and these extracardiac tissues.
- Further research is needed to determine if increased extracardiac ANP contributes to preventing bowel wall edema in CHF.
Objectives:
The present investigation was designed to determine if atrial natriuretic peptide (ANP) gene expression increases in extracardiac as well as within the heart in congestive heart failure.
Methods:
Congestive heart failure (CHF) was induced by producing cardiac hypertrophy secondary to an aortocaval fistula in Sprague-Dawley rats. To characterize this model, control and CHF rats had cardiac catheterizations and transthoracic echocardiography. ANP messenger RNA was measured by RNAase protection analysis in atria, ventricles, liver, colon, and stomach of CHF and sham rats and quantitated by 2-D scanning. The product of ANP gene expression was determined in each of these tissues with high performance-gel permeation chromatography. To help determine if increased degradation of atrial natriuretic peptides occur in congestive heart failure, the circulating concentrations and the excretion of the atrial natriuretic peptides into urine were measured by specific radioimmunoassays.
Results:
ANP steady-state mRNA increased 4.2 +/- 0.05 and 4.3 +/- 0.06-fold, respectively, in the antrum of the stomach and within the heart ventricle of CHF rats compared with age-matched sham rats. ANP gene expression was present but not increased in atria, liver, and gastrointestinal tract of the CHF rats. High-performance gel permeation chromatography revealed that the product of this ANP gene expression within the stomach and heart ventricle in CHF animals was the ANP prohormone. There was not any decrease in the metabolism of these peptides by the kidney in CHF.
Conclusions:
ANP steady-state mRNA increases in extracardiac (i.e., stomach antrum) tissue as well as in the ventricle of the heart in CHF. The product of the ANP gene expression, i.e., the ANP prohormone is the same in the extracardiac tissues as within the heart. Whether the increased extracardiac ANP steady-state mRNA and its resultant increased atrial natriuretic peptides helps prevent bowel wall edema in CHF needs to be elucidated.