The effects of the a-adrenergic agonist methoxamine on the human hypothalamic-pituitary-adrenal axis was assessed by a placebo-controlled study in the morning and one in the evening. A 5-mg iv bolus dose of methoxamine in normal subjects caused a significant rise in plasma ACTH and cortisol concentrations in the morning study. However, no significant change in plasma cortisol or ACTH concentrations was noted during the evening study. These studies suggest the existence of a diurnal variation in α1-adrenergic regulation of the hypothalamic- pituitary-adrenal axis.

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