Adrenal medullary epinephrine secretion: effects of cortisol alone and combined with aminoglutethimide.
Adrenal E synthesis is thought to require locally high glucocorticoid concentrations to induce the enzyme PNMT for methylation of NE. By suppressing ACTH secretion, exogenous glucocorticoids may limit secondarily adrenal medullary E production. AG, a competitive inhibitor of adrenal steroidogenesis, also may limit adrenal medullary E synthesis. In the present study, three groups of male beagles (mean wt. 9.45 kg) were studied with controlled endotracheal ventilation (98% O2/2% CO2) under Na pentobarbital anesthesia after a 2-week period during which group 1 (N = 4) received no drug, group 2 (N = 5) received C (0.5 mg/kg b.i.d.), and group 3 (N = 4) received C (0.5 mg/kg b.i.d.) and AG (20 mg/kg b.i.d.). Adrenal medullary secretions of E and NE were determined (single isotope radioenzymatic assay) at 15 min intervals over 1 hr basal period and 15 and 30 min following rapid hemorrhage to 50 mm Hg mean arterial pressure. Mean resting adrenal medullary E secretion of group 1 (0.576 +/- 0.181 (1 S.D.) micrograms/min) exceeded that of group 2 (C) (0.150 +/- 0.026 micrograms/min, p < 0.01) and group 3 (C and AG, (0.144 +/- 0.071 micrograms/min, p < 0.01). Maximum E secretion after hemorrhage was higher in group 1 (3.450 +/- 1.990 micrograms/min) than in group 2 (0.649 +/- 0.300 micrograms/min, p < 0.05) and group 3 (0.717 +/- 0.129 micrograms/min, p < 0.05). Highest measured E concentration after hemorrhage was also lower in treated groups (C, p < 0.01) (C and PG p < 0.01). C recipients also had suppressed resting and early reflex (p < 0.01) NE secretion. These results are consistent with the functional importance of the intimate anatomic relationship between the adrenal cortex and medulla. A defect in E-related adrenergic reflexes may occur in patients treated similarly to these experimental groups.
D000313:Adrenal Medulla / Q000378:metabolism*; D000616:Aminoglutethimide / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000503:physiopathology; D004285:Dogs; D004837:Epinephrine / Q000378:metabolism*; D006854:Hydrocortisone / Q000494:pharmacology*; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D012769:Shock / Q000503:physiopathology
D000616:Aminoglutethimide; D006854:Hydrocortisone; D009638:Norepinephrine; D004837:Epinephrine