title: Influence of exogenous atrial natriuretic peptide on the pituitary-adrenal response to corticotropin-releasing hormone and vasopressin in healthy men.
abstract: Atrial natriuretic peptide (ANP) has been considered a potential candidate participating in the inhibitory control of pituitary-adrenal secretory activity. Here, we investigated the influence of ANP, infused at two different doses and over infusion intervals of two different durations, on the release of ACTH and cortisol after stimulation with CRH and with combined administration of CRH and vasopressin (VP). In young healthy men, three experiments were conducted. In Exp I, ACTH/cortisol secretory responses to CRH (50 microg) were examined during and after a 45-min period of ANP infusion at a rate of 4.4 microg/min (starting 15 min before CRH injection). In Exp II, ACTH/cortisol secretory responses to CRH (50 microg) were examined during and after a 90-min infusion period of ANP administered at rates of 4.4 and 8.8 microg/min. In Exp III, ANP was infused at a rate of 4.4 microg/min over 90 min, but instead of CRH, a combined administration of CRH (50 microg) and VP (0.5 IU infused within 5 min) was employed to stimulate ACTH/cortisol release. ANP diminished pituitary-adrenal secretory responses within the first hour after stimulation with exogenous secretagogues. Thereafter, the effect of ANP turned in the opposite direction, with distinctly enhanced concentrations of ACTH and cortisol during the third hour after stimulation. The inhibitory effect of ANP during the first hour of the pituitary-adrenal response was more pronounced on concentrations of cortisol than ACTH and was also more pronounced after combined administration of CRH/VP than after stimulation with CRH alone. Increasing the dose of ANP enhanced the late stimulatory effect on ACTH/cortisol release, thereby terminating the early period of inhibited ACTH/cortisol release more abruptly. The late stimulatory effect was enhanced with prolonged infusion of ANP. In addition, it was associated with reduced hematocrit, increased urine volumes collected, increased heart rate, and enhanced plasma VP concentrations. Together, these changes suggest that the late stimulatory effect of ANP on ACTH/cortisol release reflects an effect secondary to its hypovolemic actions. This stimulatory effect originating from peripheral systemic actions of ANP after exogenous administration appears to override a more direct inhibitory action of the peptide on pituitary-adrenal secretory activity. Therefore, we would expect that with localized release into portal hypophyseal blood the inhibitory component of the action of ANP on pituitary-adrenal secretory activity prevails.
authors.affiliation: Clinical Neuroendocrinology and Department of Internal Medicine, University of Lübeck, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Bierwolf
authors.forename: A
authors.initials: A
authors.lastname: Burgemeister
authors.forename: K
authors.initials: K
authors.lastname: Lüthke
authors.forename: J
authors.initials: J
authors.lastname: Born
authors.forename: H L
authors.initials: HL
authors.lastname: Fehm
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000328:Adult; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism*; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D008297:Male; D010913:Pituitary-Adrenal System / Q000187:drug effects*; D012016:Reference Values; D012636:Secretory Rate / Q000187:drug effects; D014667:Vasopressins / Q000378:metabolism*
chemical_list: D014667:Vasopressins; D009320:Atrial Natriuretic Factor; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D006854:Hydrocortisone