APStracts 2:0113H, 1995.

Age-associated increase in rat ventricular anp gene expression correlates with cardiac hypertrophy . Younes, Antoine, Marvin O. Boluyt, Lydia O'neill, Andrea L. Meredith, Michael T. Crow, and Edward G. Lakatta. Gerontology Research Center, Baltimore, MD 21224, and Institut Universitaire de Technologie de Clermont-Ferrand, B.P. 86 63172 Aubiere Cedex, France.

APStracts 2:0113H, 1995.

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). Since 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 (ir-ANP) in atria, LVs and plasma of rats at 2, 6, 18 and 22-24 mo of age. Compared to LVs of 6 mo rats, the LV/BW ratio was elevated 30% by 18 mo of age, while levels of ANP mRNA were elevated 2-fold (NS) and 7-fold (P < 0.05) in the LV of 18 and 22 -24 mo rats, respectively. The concentration of ir-ANP exhibited a 4 -5-fold increase in LVs of 18 and 22-24 mo rats compared to values for 6 mo rats (43+/-4 pmol/g wet wt.; mean +/- SE). Among 18 and 22-24 mo rats a significant correlation was observed between ANP peptide concentration and LV hypertrophy (r2=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 to the 6 mo value of 9.7+/-1.9 fmol/ml, but were intermediate at 22 mo of age (16.8+/-1.5). 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.

Received 1 August 1994; accepted in final form 20 March 1995.
APS Manuscript Number H673-4.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on  4 April 1995.