Effect of a Synthetic Substituted α1-18 ACTH on Mineralocorticoid Secretion

Abstract

The effect of a synthetic long acting corticotropin (al-18 ACTH) on glucocorticoid and mineralocorticoid function and water and electrolyte balance in normal subjects has been studied. 0.5 mg of al-18 ACTH was administered i.v. to 4 normal subjects for 3 consecutive days. Plasma Cortisol (F), corticosterone (B), deoxycorticosterone (DOC) aldosterone and renin activity (PRA) were measured, at various intervals: on the preceding day, on the 3 days of therapy and on the following day. Urinary 17-OH steroids and aldosterone as well as water and electrolyte balance were also evaluated.Results: on the first day of treatment, F, B and DOC increased to their maximal values 2-4 hours after administering the drug and remained at this level for 10 hours thereafter. The values remained above basal values even on the following morning. The higher values of F and DOC were reached on the 2nd day of therapy, whereas B did not show any further increase.The plasma aldosterone showed a net increase after 4 hours on the first day but had little variation on the second day and remained unchanged or lowered on the third day as did the urinary aldosterone. PRA was not modified; there was a slight reduction in serum potassium concomitant with a decrease of urinary sodium/potassium ratio.The blood pressure remained more or less unchanged.Conclusion: the corticostimulatory action of al -18 ACTH seemed to be protracted over a 24 hour period. The therapeutic implications are discussed.

Role of adrenocorticotropic hormone in essential hypertension and primary aldosteronism

“…The major physiological regulators of aldosterone production from the adrenal glomerulosa are potassium, angiotensin II, ACTH, and serotonin . The aldosterone synthase (CYP11B2) activity is dependent on angiotensin II, but it is well known that acute ACTH administration increases plasma aldosterone . The duration of ACTH administration is important since prolonged stimulation with ACTH suppresses aldosterone.…”