We have shown previously that the hearts of aging rodents exhibit hypertrophy at both the organ and cellular (myocyte) levels. We have also shown that the senescent heart shares a number of attributes with the hypertensive heart, including slowed contraction dynamics, increased stiffness, increased expression of ANF mRNA.
The aims of this project were to 1) determine whether ANF peptide levels were altered in parallel with mRNA in the various chambers of the heart, 2) whether the increased stiffness of myocardium observed in advanced age was associated with increased expression of fibronectin, and 3) whether expression of immediate early genes was augmented in the heart during aging from adulthood through senescence. ANF peptide concentrations were determined by radioimmunoassay in left ventricular tissues of 2, 6, 18 and 22-24 mo Wistar rats. Total RN was isolated from hearts of Wistar rats of the same ages. The concentratio of ir-ANF in the LV increased w4-5-fold in LVs of 18 and 22-24 mo rats compared to values for 2 mo (35q5 pmol/g wet wt.; mean q SE) and 6 mo (43q4 rats. Among 18 and 22-24 mo rats a significant correlation was observed between ir-ANF concentration and LV hypertrophy (r2=0.64). Left atrial concentrations of ir-ANF were lowest at 18 mo of age (62q8 nmol/g wet wt.), and significantly elevated at 22 mo of age (2.7-fold). In contrast, plasma ir-ANF concentrations were 2.4-fold higher at 18 mo of age compared to the 6 mo value of 9.7q1.9 fmol/ml. Levels of ANF mRNA were elevated 2-fold (NS and 7-fold (P < 0.05) in the LVs of 18 and 22-24 mo rats, respectively, while levels in pooled samples of atria were 2-fold greater for 22-24 mo compared to 2 mo rats. The levels of fibronectin mRNA were elevated 4-fold in 24 vs. 6 mo rats. The levels of c-jun mRNA increased 2-fold between 6 and 24 mo of age, while fos and junB were not different among the ages studied. Levels of the constitutively expressed hsp70 mRNA were elevated 2 fold in hearts of 24 vs. 6 mo rats. The marked changes in LV ANF gene expression with advancing age suggest that LV endocrine release may contribute significantly to circulating ANF levels in the senescent rat. The increased levels of fibronectin mRNA provide a link between extracellular matrix gene expression the increased stiffness of cardiac muscle observed previously. The increased levels of hsp70 and c-jun mRNA suggest that at least some cells may be acutely stressed in the senescent heart.
