Atrial natriuretic factor inhibits the CRH-stimulated secretion of ACTH and cortisol in man

Abstract

Corticotrophic secretion of ACTH is stimulated by corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP), and suppressed by glucocorticoids. In vitro and preclinical studies suggest that atrial natriuretic factor (ANF) may be a peptidergic inhibitor of pituitary-adrenocortical activity. The aim of this study was to elucidate a possible role of ANF as a modulator of ACTH release in humans. A bolus injection of 100 μg human CRH (hCRH) during a 30 min intravenous infusion of 5 μg/min human alpha atrial natriuretic factor (gαANF) was administered at 19:00 to six healthy male volunteers. In comparison to saline, a blunted CRH-stimulated secretion of ACTH (mean maximum plasma level ± SD 45 min after hCRH: saline 46.2±14.2 pg/ml, hαANF 34.6±13.8 pg/ml, p-value = 0.007) and a delayed rise (10 min) in cortisol were detected. The maximum plasma cortisol levels remained nearly unchanged between saline and hαANF administration (mean maximum plasman level ± SD 60 min after hCRH: saline 182±26 ng/ml, hαANF 166±54 ng/ml). No effects of hαANF on basal cortisol levels were observed; in contrast, basal ACTH plasma levels were slightly reduced. Basal blood pressure and heart rate remained unaffected. In the control experiment, infusion of 3 IU AVP in the same experimental paradigm increased basal and stimulated ACTH and cortisol levels significantly in comparison to saline. These observations suggest that intravenously administered haANF inhibits the CRH-stimulated release of ACTH in man.