The sensitivity of adrenal responses to synthetic adrenocorticotrophin in the conscious unrestrained calf.

Abstract

1. Changes in cortisol and corticosterone output and blood flow from the adrenal gland have been determined in the conscious unrestrained calf during I.V. infusions of synthetic adrenocorticotrophin (Synacthen) at 0-5 ng-kg(-1) min- minus 1 (low dose), 5 ng-kg- minus 1 (medium dose), 50 ng-kg- minus 1 min- minus 1 (high dose) and 500 ng-kg- minus 1 min- minus 1 (medium dose), 50 ng-kg- minus 1 min- minus 1 (high dose) and 500 ng-kg- minus 1 min- minus 1(very high dose). 2. Infusions at the low dose produced a rise in adrenal output of both cortisol and corticosterone to maximum values of approximately 100 and 30 ng-kg- minus 1 min- minus 1 respectively. Mean output of both steroids was significantly increased within 5 min, reached a maximum within 10 min and had fallen to resting levels 10 min after the infusion was discontinued. 3. The effects of infusions at both the high and very high doses were closely similar; maximal cortisol outputs were within the range 600-800 ng-kg- minus 1 min- minus 1 and corticosterone 350-500 ng-kg- minus 1 min- minus 1 in both groups. 4. When the infusions were terminated, pronounced differences were observed in the rates at which steroid outputs declined. Basal levels were restored within 10 min following the low dose and within 60 min in medium dose animals, but both cortisol and corticosterone output were still elevated 2 hr after infusion in high dose animals. In calves infused at the very high dose, cortisol output did not fall significantly during 2 hr period. The ratio of cortisol: corticosterone released from the adrenal gland immediately before infusion (3-2 +/- 0-3) approximated to the proportions in which the two steroids were found in the arterial plasma, but fell progressively to a minimum (1-3 +/- 0-1) with increasing doses of Synacthen. Conversely, the ratio of the steroids in the arterial plasma was increased during infusions at the low dose, but not at the higher doses. 6. No significant change in adrenal blood flow occurred during Synacthen infusion in low dose animals despite the increase in steroid output. In medium dose animals blood flow through the gland rose during infusion by approximately 75 per cent while in both high and very high dose animals the flow increased by up to 300 percent. 7. In the three groups in which adrenal hyperaemia occurred, blood flow had fallen to within the resting range 45 min after infusion: in each case this fall was much more rapid than the fall in steroid output. No significant increase in aortic blood pressure or heart rate accompanied infusion of Synacthen, indicating that adrenal hyperaemia was dependent upon vasodilatation with the gland. 8. Administration of cycloheximide (10 mg/kg) by I.V. injection either before or during an infusion of Synacthen, inhibited steroidogenesis without affecting the vasodilator response.