Pressure overload induces heterologous expression of the atrial natriuretic factor (ANF) gene

Several investigations have demonstrated the regional heterogeneity of myocardial phenotype, and hypertrophy may also induce regionally disparate changes. We have utilized the direct DNA injection technique to study regional variations in overload-induced ANF expression. Pressure overload was induced by stenosis of the ascending aorta in canines. ANF promoter reporters were injected into the left ventricle; in different regions including the base, the midwall region, and the apex. Injections were made at different depths to include the epicardial and endocardial layers. The animals were sacrificed 7 days following surgery and the left ventricle harvested for tissue analysis. Under normotensive conditions, ANF reporter expression was similar throughout the heart. PO increased ANF expression and the increases were greater in the endocardium than in the epicardium. PO also significantly increased expression in the midwall and base regions, but not in the apex. It is unknown from these experiments, whether the greater increases in midwall expression are a function of greater wall stress, metabolic demand, or phenotypic differences in the midwall myocytes. These findings do indicate that regional differences in overload-induced changes in gene expression are evident and may be functionally important in determining myocardial response to increased functional demand.