Effect of adrenocortical steroids and their structural analogues on blood pressure in sheep

1. A model of adrenocortical steroid-induced hypertension based on the effects of ACTH administration has been developed in sheep. The present studies examine the effects of a number of different steroid hormones on blood pressure to investigate their structure-activity relationships. 2. Infusion of the major ovine adrenal steroid hormones (combined steroid infusion of cortisol, corticosterone, 11-deoxycortisol, aldosterone, deoxycorticosterone) reproduced the metabolic but not the blood pressure effects of ACTH. 3. Addition of 17 alpha, 20 alpha-dihydroxyprogesterone and 17 alpha-hydroxyprogesterone, at rates appropriate for conditions of ACTH stimulation, to the combined steroid infusion reproduced both the blood pressure and metabolic effects of ACTH. 4. 17 alpha-20 beta-Dihydroxyprogesterone, 20 beta-dihydroxy-11-deoxycortisol and 20 beta-hydroxycortisol all had additional hypertensive activity when given with combined steroid infusion, but 16 alpha-hydroxyprogesterone, 11 beta, 17 alpha-dihydroxyprogesterone, 20 alpha-hydroxyprogesterone and 20 beta-hydroxyprogesterone did not. 5. These studies support the concept of a new class of steroid hormone action in blood pressure regulation.