Improvement of sleep and pituitary-adrenal inhibition after subchronic intranasal vasopressin treatment in elderly humans.

Subchronic intranasal treatment with argininevasopressin (AVP) has been shown to exert a strong ameliorating effect on sleep and slow wave sleep (SWS) deficits in elderly. However, AVP is also a potent stimulus of the pituitary-adrenal stress system, which is usually inhibited during early, SWS-rich sleep. A disinhibition of pituitary-adrenal activity during sleep is correlated with aging and is considered a pathologic factor contributing to various age-related diseases. Here, we examined whether the beneficial effect of prolonged intranasal AVP administration on sleep in aged would be associated with a concomitant decrease in pituitary-adrenal inhibition and effects on other neuroendocrine features of sleep. Twenty-six healthy elderly (mean 72.9 yr) with mild sleep complaints were investigated in a placebo controlled double-blind study. One group was treated daily each morning and evening with intranasal AVP (2 x 20 IU) for 10 weeks, the other received placebo. During polysomnographical recordings taken at the beginning and end of the treatment period, blood was sampled every 15 min. Intranasal AVP increased SWS on average by +21.5 min (p<0.02). The effect persisted on the night after acute withdrawal of the peptide treatment with no rebound occurring. Notably, rather than increasing pituitary-adrenal activity, AVP decreased the early sleep cortisol nadir on average by 0.5 microg/dl (p<0.05). AVP did not induce any measurable changes in fluid balance or cardiovascular activity. Overall, results indicate a promoting effect of AVP on SWS in aged accompanied by a beneficial rather than impairing influence on the neuroendocrine pattern of sleep.