Natriuretic and hypertensive activities reside in a fragment of ACTH

The hypertensive and natriuretic effects of chronic administration of adrenocorticotrophic hormone (ACTH) cannot be duplicated by the administration of glucocorticoids and/or mineralocorticoids. We investigated the effects of a fragment of this hormone (ACTH4-10) and an analog of the fragment (D-Phe7) ACTH4-10 and found them to have pressor and cardioaccelerator actions in rats as determined by bolus intravenous (i.v.) injections of 30 to 1000 nmol/kg. The pressor and cardioaccelerator effects of (D-Phe7) ACTH4-10 were attenuated by alpha-receptor (phentolamine) and beta-receptor (metoprolol) antagonists. The cardiovascular actions of ACTH4-10 were produced in adrenalectomized or ganglionic-blocked (with mecamylamine) rats. At a lower dose (7 nmol/kg i.v.), ACTH4-10 was natriuretic and had a pattern of activity similar to that of a larger ACTH fragment, alpha-melanocyte-stimulating hormone. Extraadrenal effects of the intact ACTH molecule or the in vivo production of an ACTH4-10-like fragment from ACTH may contribute to the hypertensive and natriuretic actions associated with this hormone.