AGE-ASSOCIATED INCREASE IN RAT VENTRICULAR ANP GENE-EXPRESSION CORRELATES WITH CARDIAC-HYPERTROPHY

Atrial natriuretic peptide (ANP), a cardiac-specific hormone, is stored in the atria and released in response to atrial stretch. During cardiac hypertrophy, ANP gene expression is markedly upregulated in the left ventricle (LV). Because the hearts of normotensive senescent rats exhibit left atrial (LA) and left ventricular (LV) hypertrophy and dilatation, we examined ANP mRNA levels by Northern blot analysis and ANP peptide concentrations by radioimmunoassay in atria, LVs, and plasma of rats at 2, 6, 18, and 22-24 mo of age. Compared with LVs of B-mo-old rats, the LV-to-body weight ratio was elevated 30% by 18 mo of age, whereas levels of ANP mRNA were elevated twofold (not significant) and sevenfold (P < 0.05) in the LV of 18- and 22- to 24-mo-old rats, respectively. The concentration of immunoreactive ANP (ir-ANP) exhibited a four- to fivefold increase in LVs of 18- and 22- to 24-mo-old rats compared with values for 6-mo-old rats (43 +/- 4 pmol/g wet wt; means +/- SE). Among 18- and 22- to 24-mo-old rats a significant correlation was observed between ANP peptide concentration and LV hypertrophy (r(2) = 0.64). Levels of ANP mRNA and ir-ANP in the atria exhibited only modest changes with aging. Plasma ir-ANP concentrations were 2.4-fold higher at 18 mo of age compared with the 6-mo value of 9.7 +/- 1.9 fmol/ml but were intermediate at 22 mo of age (16.8 +/- 1.5 fmol/ml). Given the size of the LV relative to the atria, these data suggest LV endocrine release may contribute significantly to circulating ANP levels in the senescent rat. The correlation between ir-ANP and hypertrophy in the LVs of older rats suggests that a common mechanism(s) is responsible for the age-associated increases in ANP gene expression and cardiac hypertrophy.