High intensity venous sampling reveals subtle alterations in plasma adrenocorticotropin patterns in old rats

Dysregulation of the hypothalamic-pituitary-adrenocortical axis has been theoretically linked to the processes of aging for decades. To investigate the effects of age on high frequency rhythms of plasma ACTH at the time of circadian activation, integrated 2-min blood samples were collected over 4 h in 10 young and 14 old rats with simultaneous plasma volume replacement. Plasma ACTH time series were analyzed in the time and frequency domains. Relative to young rats, old rats had a significantly later onset of the diurnal surge, more spectral power (R2) at lower frequencies, a lack of correlation between the slope of the spectral background continuum and the R2 at periods less than approximately 11 min, a stretching of the time scale in the composite spectra by 18.5%, and an amplitude reduction of the major composite spectral peak by 31%. These findings support the existence of subtle, but significant, alterations in the pattern of plasma ACTH with age and a delayed response of the hypothalamic-pituitary-adrenocortical axis to circadian activation. The differences in spectra suggest a weaker coupling with age between the high frequency signal input (that may reflect depolarization of groups of corticotrophs) and the system response, which could account for the delay in onset of the diurnal surge seen in the time domain.