Hypoglycemia attenuates cardiovascular homeostatic autonomic control. This attenuation, known as the cardiovascular component of hypoglycemia associated autonomic failure (HAAF) is characterized most notably by decreased baroreflex sensitivity (BRS) that begins during hypoglycemia and persists until at least the next day, despite return to euglycemia. Understanding the mechanisms underlying this reduction in BRS is important since BRS attenuation is associated with increased morbidity and mortality.Investigate the role of the adrenocorticotropin hormone (ACTH)-adrenal axis in decreasing BRS. We tested the hypothesis that infusion of ACTH 1-24 (cosyntropin), as compared to placebo, would acutely suppress BRS, and that this decrease in BRS would be present the next day.Double-blind, placebo-controlled, random-order, cross-over study.Clinical research center.Healthy men and women.Intravenous infusion of cosyntropin (70 mcg/hour for 2.5 hours in the morning and again in the early afternoon) versus normal saline placebo.BRS during and 16 hours after cosyntropin versus placebo infusions.Cosyntropin infusion attenuated BRS (mmHg/ms) as compared to placebo (baseline 17.8±1.38 vs.17.0±2.07; during 14.4±1.43 vs. 17.3±1.65; and next day 14.8±1.42 vs. 18.9±2.04; p<0.05, time by treatment, ANOVA). BRS was decreased during the final 30 minutes of the AM cosyntropin infusion as compared to baseline (p<0.01) and remained suppressed the next day (16 hours after PM infusion) (p<0.025). Placebo infusion did not significantly change BRS. QTc was not affected.ACTH attenuates BRS, raising the possibility that hypoglycemia-induced increases in ACTH may contribute to the cardiovascular component of HAAF.