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. In addition we studied differences in the response of ANF mRNA levels to aortic constriction in hearts of young adult and senescent rats. Total RNA was isolated from left ventricles (LV) 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. The induction of the ANF gene in ventricles of aortic-constricted rats was blunted with advancing age. Since ANF peptide is known to affect cardiomyocyte function, the age-associated increase in ANF gene expression may be of functional importance in the senescent heart.
