Atrial natriuretic factor (ANF) is synthesized and secreted by atrial tissue in response to experimental or genetic hypertension. Recent studies have shown that ANF is produced and secreted by left ventricular tissue as well, and that ANF has direct effects on ventricular cardiac myocyte contraction. Since heart contractile function is altered during aging, and the senescent heart exhibits many other phenotypic and genotypic characteristics of the hypertensive heart, we tested the hypothesis that the atrial natriuretic factor (ANF) gene would be upregulated with advancing age. Since progressive age-associated myocyte hypertrophy is evident in left ventricle (LV) of the Wistar, but not in the LV of F344 nor in the right ventricle (RV) of either strain, total RNA was isolated from the LV and RV of male Wistar and Fischer rats aged 1.5-27 mo of age. Northern blots were probed with a radiolabeled cDNA probe synthesized by PCR using oligonucleotides complementary to the published sequence. The levels of mRNA coding for ANF increased progressively with advancing age in ventricles of both strains of rats. ANF mRNA abundance was 7-fold greater in ventricles of senescent compared to young adult rats. In freshly isolated ventricular myocytes, a similar pattern was observed. ANF mRNA levels were not augmented during aging in the atria of Wistar rats. In contrast to the age-associated increase in ventricular ANF mRNA levels, the concentration of ANF peptide in the LV decreased with advancing age, suggesting that either secretion or degradation rates are increased in the ventricles during aging. To obtain an indication of hemodynamic stress, expression of early response genes was assessed. Levels of both heat shock protein (hsp70) and c-jun mRNAs were elevated approximately 2-fold in hearts of some, but not all senescent rats, compared to those of young adult rats. c-fos and junB mRNAs were not elevated in any of the hearts studied. The low level induction of hsp70 and c-jun gene expression in some senescent hearts, suggests that a subpopulation of myocytes and/or fibroblasts may be stressed in the aging heart. Since in F344 LV and in the RV of both strains the age- associated elevation in ANF occurs in absence of myocyte hypertrophy, these results suggest that an in-dependent age-related mechanism exists to regulate ANF gene expression in the ventricles. Further study is required to identify factors regulating ANF gene expres-sion in the ventricles during aging, and to determine the fate of ANF peptide in the senescent heart.
