The stress response involves activation of the hypothalamic-pituitary adrenal axis and the sympathetic nervous system. To study the relative contributions of glucocorticoids, epinephrine, norepinephrine, and dopamine to homeostasis, we examined the effects of cortisol and epinephrine deficiency on the norepinephrine and dopamine responses to surgical stress in nonhuman primates. Adult male cynomolgus monkeys (n = 7-8/group)underwent bilateral or sham adrenalectomy and were maintained for 4 months on physiologic glucocorticoid (hydrocortisone phosphate, 32 mg/M2/day) and mineralocorticoid (DOCA pivalate, 1 mg/day) replacement, or placebo injections, respestively. The adrenalectomized monkeys were then stratified into three groups receiving subphysiologic (× 1 10), physiologic (×1), or supraphysiologic (×10) glucocorticoid replacement. A cholecystectomy was performed 4 days later and the pre-, intra-, and postoperative plasma catecholamine levels were measured. Adrenalectomized animals had markedly decreased plasma epinephrine concentrations and accentuated plasma norepinephrine and dopamine responses to cholecystectomy, when compared to shamadrenalectomized controls. The magnitude of the norepinephrine accentuation was inversely related to the dose of cortisol administered preceding surgery. Norepinephrine and dopamine failed to completely normalize even at the high dose of glucocorticoid replacement which had been calculated to be similar to the cortisol production rate during maximal stress. Thus, surgical stress in the setting of inadequate glucocorticoid (cortisol) replacement and epinephrine deficiency, stimulates additional sympathetic activity, probably as an adaptive mechanism to maintain homeostasis. Both norepinephrine and dopamine are recruited to compensate for the glucocorticoid and epinephrine deficiency. Glucocorticoid administration decreases but does not normalize this compensatory sympathetic activity.
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