Atrial natriuretic peptide (ANP), originally found in the cardiac atria, is also widely distributed in the central nervous system (CNS) and has been predominantly found in the hypothalamus and the pituitary gland. Previous in vitro and in vivo studies have provided evidence for an inhibitory control of ANP at all regulatory levels of the hypothalamo-pituitary-adrenocortical (HPA) system. In vivo studies in man demonstrated that ANP inhibits stimulated pituitary-adrenal secretion during wakefulness. On the other hand, it has been reported that various neuropeptides not only influence the neuroendocrine compound of sleep, but also exert specific effects on the sleep electroencephalogram (EEG). To further characterize the role of ANP in the regulation of the nocturnal HPA axis activity and consecutive sleep regulation, we investigated sleep-endocrine effects of intravenously administered ANP in healthy men during nocturnal sleep. Eight volunteers underwent three trial conditions in random order and in a single-blind design receiving ANP infusion at the beginning of the 1st or the 2nd half of the night, or placebo. Sleep was assessed by polysomnography and blood samples were drawn in 30-min intervals for determination of adrenocorticotrophic hormone (ACTH) and cortisol during the entire night. While the ACTH and cortisol secretion during ANP infusions remained unchanged, an immediate increase of ACTH and cortisol secretion occurred after each infusion period for approximately 2h without changing basal levels and the circadian course of both hormones. Sleep EEG parameters were neither directly affected by ANP infusions nor by the following ANP-induced ACTH and cortisol secretion. The presence of such clear-cut enhancement of the pituitary-adrenal release indicates a rebound effect of ANP on HPA secretory activity and supports the idea that ANP acts as corticotropin-releasing hormone (CRH)-inhibiting factor.
