Evidence for altered hypothalamus-pituitary-adrenal axis functioning in systemic hypertension: blunted cortisol response to awakening and lower negative feedback sensitivity

Psychoneuroendocrinology. 2007 Jun;32(5):430-6. doi: 10.1016/j.psyneuen.2007.02.006. Epub 2007 Apr 11.


Background: Hypothalamus-pituitary-adrenal (HPA) axis functioning in systemic hypertension is not fully understood. We explored HPA axis activity and feedback sensitivity to oral administration of dexamethasone in systemic hypertension via assessment of the cortisol awakening response (CAR) and the circadian cortisol profile.

Methods: The CAR and circadian cortisol profile were assessed in 20 unmedicated and otherwise healthy middle-aged hypertensive men and in 22 normotensive male controls. Salivary free cortisol measures for the CAR were obtained immediately after awakening and 15, 30, 45, and 60 min thereafter. Circadian cortisol secretion was sampled at 08:00, 11:00, 15:00, and 20:00 h. Assessment of the CAR was repeated on the next day after administration of 0.5mg dexamethasone at 23:00 h on the previous night.

Results: Hypertensives had a significantly lower CAR (p<0.02) and significantly reduced suppression of the CAR after dexamethasone administration (p<0.01) than normotensive controls. There were no significant differences in cortisol levels at awakening and in circadian cortisol profiles between hypertensives and normotensives.

Conclusion: We found evidence for altered HPA axis activity in men with systemic hypertension evident with the CAR. Hypertensives showed relative attenuation in the CAR and in the HPA axis feedback sensitivity following dexamethasone suppression. Such alterations in HPA axis regulation might contribute to the atherosclerotic risk in hypertensive individuals.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Circadian Rhythm / physiology*
  • Dexamethasone / pharmacology
  • Feedback, Physiological / drug effects
  • Feedback, Physiological / physiology*
  • Glucocorticoids / pharmacology
  • Humans
  • Hydrocortisone / metabolism*
  • Hypertension / metabolism*
  • Hypothalamo-Hypophyseal System / drug effects
  • Hypothalamo-Hypophyseal System / metabolism
  • Male
  • Middle Aged
  • Pituitary-Adrenal System / drug effects
  • Pituitary-Adrenal System / metabolism
  • Reference Values
  • Saliva / metabolism
  • Statistics, Nonparametric
  • Wakefulness / physiology*


  • Glucocorticoids
  • Dexamethasone
  • Hydrocortisone