Adrenal Sensitivity to Adrenocorticotropin in Normovolemic and Hypovolemic Conscious Dogs*

Abstract

In the preceding paper we reported that conscious dogs respond to 15 ml/kg hemorrhage with increases in plasma corticosteroids that are often unaccompanied by measured increases in plasma ACTH. These experiments were designed to test for a hemorrhage-induced shift in adrenal sensitivity to ACTH. Hemorrhage-induced changes in adrenal sensitivity were tested in two ways. First, dexamethasone-pretreated dogs were subjected to four 5-min steps of ACTH infusion, increasing in rate from 38 to 380 ng/min. The increasing rates of ACTH infusion elevated plasma ACTH to levels that were linearly related to the ACTH infusion rate, and elevated plasma corticosteroids to levels that were linearly related to the logarithm of the ACTH infusion rate and the plasma ACTH concentration. The magnitude of the peripheral plasma corticosteroid response to the ACTH step infusion was not changed either by simultaneous hemorrhage or by step infusion or hemorrhage 1.5–2 h earlier. Second, dexamethasone-pretreated dogs were subjected to 30-min infusions of ACTH at constant rates of 5, 10, or 20 ng/min. The infusions elevated plasma ACTH to levels that were linearly related to the infusion rate, and plasma corticosteroids increased to levels linearly related to the logarithm of the ACTH infusion rate. This dose-response relationship was not altered significantly by simultaneous 15 ml/kg hemorrhage and hypovolemia. However, during these infusion experiments, it was found that the cortisol distribution volume may increase during the first 10 min of hemorrhage-induced hypovolemia. The steady state infusions of ACTH demonstrate that the adrenals are normally very sensitive to small increases in plasma ACTH. However, because an increase in cortisol distribution volume may occur during hypovolemia, and peripheral levels of corticosteroids are the same in response to ACTH infusion in the presence and absence of hypovolemia, the adrenal sensitivity to ACTH or the ACTH presentation rate to the adrenal may increase during hemorrhage-induced hypovolemia in the conscious dog.