ADRENOCORTICAL STEROID REQUIREMENTS FOR INITIATION OF ACTH‐DEPENDENT HYPERTENSION IN SHEEP

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Abstract
1. Previous studies demonstrated that the combined infusion of cortisol (F), aldosterone (ALDO), deoxycorticosterone (DOC), corticosterone (B), 11‐deoxycortisol (S), 17α‐hydroxyprogesterone (17αOHP) and 17α, 20α‐dihydroxy‐4‐pregnane‐3‐one (17α20αOHP), at rates equivalent to their production during adrenocorticotrophic hormone (ACTH) treatment, reproduced the pressor and metabolic responses to ACTH administration in sheep. 2. This study examined which of these adrenocortical steroids were necessary for the initiation of the hypertension produced by these steroids in sheep. 3. Infusion of F, ALDO, 17αOHP and 17α20αOHP together, increased MAP by 19 mmHg, similar to both complete steroid cocktail (+25 mmHg) or ACTH administration (+ 21 mmHg). Infusion of F, 17αOHP and 17α20αOHP increased MAP by +7 mmHg. Infusion of ALDO, 17αOHP and 17α20αOHP had no effect on MAP. Thus F and ALDO were essential for the pressor effects of the steroid infusion. 4. To determine the role of glucocorticoid activity in the MAP rise, prednisolone, a non‐pressor glucocorticoid, was substituted for cortisol. Combined prednisolone, ALDO, 17αOHP and 17α20αOHP infusion did not raise blood pressure. This suggested that the mineralocorticoid component rather than glucocorticoid component of cortisol's activity was involved in the pressor response. 5. Aldosterone (7 μg/h) was substituted for cortisol, giving a total of 10 μg/h aldosterone. High dose ALDO (10 μg/h), 17αOHP and 17α20αOHP infusion raised blood pressure by 18 mmHg. Thus, the essential role of cortisol appeared to be due to its occupancy of mineralocorticoid receptors, rather than glucocorticoid receptors. 6. Given that ACTH produces a transient initial increase in aldosterone secretion of up to 10 μg/h, it appears that aldosterone and not cortisol is essential for the pressor effects of ACTH. 7. Hypertension resulting from the combined steroid infusion in the sheep appears to be produced by a mechanism which involves a complex interaction between ALDO, F, 17αOHP and 17α20αOHP. Therefore, the putative ‘hypertensinogenic’ receptor may be multivalent with binding sites for F, ALDO and 17α20αOHP, or is a site of single interactive receptors for these steroids and that F exerts its permissive action by occupying the same site as ALDO on the hypertensinogenic receptors.