Onset and dose relationships of ACTH effects on blood pressure in sheep

The threshold and dose-response relationships for the blood pressure and metabolic effects of adrenocorticotropic hormone (corticotropin, ACTH) were examined in conscious sheep. Corticotropin was infused at five rates (0.5 micrograms/kg/day, n = 4; 1 micrograms/kg/day, n = 4;2 micrograms/kg/day, n = 6; 5 micrograms/kg/day, n = 5; and 10 micrograms/kg/day, n = 5) for 3 days, and the time of onset of the rise in blood pressure was assessed with a computer-based system. The effects of equimolar infusion of beta-endorphin and ACTH at 5 micrograms/kg/hour also were examined. Corticotropin infusion at 0.5 microgram/kg/day had no effect on mean arterial pressure. An ACTH infusion of 1.0 microgram/kg/day significantly increased mean arterial pressure (p less than 0.001), but the rise was less than that at the three higher doses, all of which produced similar effects. Changes in heart rate were significant at the 10 micrograms/kg/day level only (p less than 0.01). Initial urinary sodium retention was present at the three higher but not the two lower rates of infusion. Corticotropin infusion had no effect on urinary potassium excretion at any rate but produced hypokalemia at rates of 1.0 microgram/kg/day and above, which appeared to be dose related. Plasma sodium concentration was increased significantly only at the three higher rates (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)