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 17α, 20α-dihydroxyprogesterone and 17α-hydroxyprogester-one, at rates appropriate for conditions of ACTH stimulation, to the combined steroid infusion reproduced both the blood pressure and metabolic effects of ACTH. 4. 17α, 20β-Dihydroxyprogesterone, 20β-dihydroxy-11-deoxycortisol and 20β-hydroxycortisol all had additional hypertensive activity when given with combined steroid infusion, but 16α-hydroxyprogesterone, 11β, 17α-dihydroxy-progesterone, 20a-hydroxyprogesterone and 20α-hydroxyprogesterone did not. 5. These studies support the concept of a new class of steroid hormone action in blood pressure regulation.