Effects of prolonged ACTH treatment on adrenal steroidogenesis and blood pressure in rats

Publisher Website
Google Scholar
Abstract
The effects of long-term (8-16 days) treatment of rats with synthetic 1-24 ACTH (100 .mu.g/day) on adrenocortical function and blood pressure were investigated. After 16 days, treated animals had considerably enlarged adrenals, a reduced body weight and systolic blood pressures of 169 .+-. 3 mmHg compared with 117 .+-. 4 mmHg in untreated controls. Corticosterone and 18-hydroxydeoxycorticosterone (18-OH-DOC) production in vitro from endogenous precursors was increased 3- to 4-fold in capsules and 1.5-fold in inner zones, whereas production of aldosterone and 18-hydroxycorticosterone was reduced. Similar increases in corticosterone and 18-OH-DOC production by capsules and inner zones were found with 12 days'' treatment, during which blood pressure increased to a constant level after 8 days. Secretion of 18-OH-DOC and corticosterone by the left adrenal gland in anesthetized rats was significantly higher in the ACTH treated group while the secretion of aldosterone was > 80% lower. The aldosterone response of dispersed capsule cells to stimulation by K (8.4 mmol/l) and ACTH (10-8 mol/l) was lost following ACTH treatment. The responses of inner zone and capsule dispersed cell preparations to ACTH (10-8 mol/l) were reduced compared with controls. Restriction of the rats'' Na intake (to < 20 .mu.mol/day) during ACTH treatment did not prevent the decrease in aldosterone production in vitro, nor the increase in blood pressure. Overall chronic ACTH treatment resulted in a marked inhibition of aldosterone production and response to stimulation coupled coupled with an increase in corticosterone and 18-OH-DOC production. ACTH apparently induces functional transformation of the glomerulosa cell to a fasciculata-like cell. Hypertension in ACTH treated rats should be related to the increased secretion of corticosterone and 18-OH-DOC and aldosterone and 18-hydroxycorticosterone apparently are not involved.

This publication has 13 references indexed in Scilit: