Atrial natriuretic peptide (ANP) is a hormone important in the cardiovascular system via its regulatory roles in sodium and water excretion, and in vasodilatation. Aging represents a major risk factor in the development of hypertension, a perturbation which may activate compensatory mechanisms. The influence of aging on the ANP levels in plasma, atria, ventricles, hypothalamus, and brainstem was evaluated by comparing young (3 mo), middle-aged (12 mo), and old (24 mo) rats. Plasma and ventricular ANP levels increased with age, while ANP content in the atria as well as hypothalamus decreased significantly. PreproANP mRNA contents increased with age in the ventricle but not in the atrium. It is suggested that the increase in plasma ANP levels in old rats is due to the increase in ANP secretion from the atrium and the ventricle, partly as a result of an increase of release of ANP from hypothalamus.A TRIA from a variety of animal species, including L humans, are characterized by the presence of membrane-bound granules (Jamieson and Palade, 1964) that are involved in opposing the development of hypertension (De Bold et al., 1981). These granules store the precursor of the atrial natriuretic peptide (ANP), a 28 amino acid peptide hormone which is synthesized and released by the atria. Several other tissues, including lung, liver, intestine (Gardner et al., 1986), and brain (Gardner et al., 1987), also synthesize small amounts of the peptide.It is well known that aging is associated with cardiovascular and endocrine disorders (Yoshikawa and Beck, 1990), and thus much attention has been paid to the etiology of cardiovascular consequences associated with aging (Julius and Schork, 1971;Berkman and Seeman, 1986). Agerelated changes of ANP have been associated with the dysfunction of the vasomotor tone and body fluid homeostasis. The plasma concentration of ANP has recently been reported to increase in older adult rats (12-18 mo) versus younger rats (2-4 mo) (Korytkowski and Landenson, 1991). The source of the increased plasma ANP levels with aging appears to be the heart (Giordan et al., 1993). As the atrium and the ventricle are important sources of ANP in the plasma, and ANP in the central nervous system may be involved in the regulation of peripheral ANP release (Charles et al., 1991), we have examined the ANP contents in the atria and the ventricle as well as the brain, and correlated these to the plasma ANP levels in young, middleaged, and old rats.
METHODSAnimals. -Male Sprague-Dawley rats aged 3, 12, and 24 months (young, adult, and old) were housed at a constant temperature (22 °C) on a 12-h dark-light cycle. Food and water were freely available.Radioimmunoassay (RIA). -To assay tissue immunoreactive ANP concentration, the atrium, ventricle, hypothalamus, and brainstem were dissected from decapitated rats, quickly frozen on dry ice, and stored at -70 °C. Tissues were homogenized in 2 N acetic acid and boiled for 10 minutes. Aliquots of 50 ul of homogenate were aspirated for protein assay. The remaining homogenate w...