CONGESTIVE-HEART-FAILURE - INCREASED CARDIAC AND EXTRACARDIAC ATRIAL-NATRIURETIC-PEPTIDE GENE-EXPRESSION

Objectives: The present investigation was designed to determine if atr ial natriuretic peptide (ANP) gene expression increases in extracardia c as well as within the heart in congestive heart failure. Methods: Co ngestive heart failure (CHF) was induced by producing cardiac hypertro phy secondary to an aortocaval fistula in Sprague-Dawley rats. To char acterize 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 st omach of CHF and sham rats and quantitated by 2-D scanning, The produc t of ANP gene expression was determined in each of these tissues with high performance-gel permeation chromatography. To help determine if i ncreased degradation of atrial natriuretic peptides occur in congestiv e heart failure, the circulating concentrations and the excretion of t he atrial natriuretic peptides into urine were measured by specific ra dioimmunoassays, 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, liv er, and gastrointestinal tract of the CHF rats. High-performance gel p ermeation chromatography revealed that the product of this ANP gene ex pression 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 inc reases 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 pre vent bowel wall edema in CHF needs to be elucidated.