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

Abstract

SUMMARY 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 jig/kg/day, n -4; 1 /ig/kg/day, n = 4; 2 /xg/kg/day, n = 6; 5 jxg/kg/day, n = 5; and 10 ^tg/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 /3-endorphin and ACTH at 5 ^ig/kg/hour also were examined. Corticotropin infusion at 0.5 ^g/kg/day had no effect on mean arterial pressure. An ACTH infusion of 1.0 /xg/kg/day significantly increased mean arterial pressure (p < 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 /xg/kg/day level only (p < 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 /xg/kg/day and above, wTiich appeared to be dose related. Plasma sodium concentration was increased significantly only at the three higher rates (p < 0.001). Urine volume and water intake were increased at ACTH infusion rates of 2.0 to 10 /xg/kg/day. Blood cortisol concentration was increased in the 1 /xg/kg/day group and was maximal in the 2 /xg/kg/day group. Blood corticosterone levels were maximal at infusion rates of 1 /xg/kg/day. A well-defined diurnal rhythm of mean arterial pressure was apparent during the 3 control days. At 10 /xg/kg/day ACTH produced an increase in mean arterial pressure within 8 hours. Infusion of equipotent amounts of ACTH and /3-endorphin did not modify ACTH-induced hypertension. These results indicate that (1) increases in blood pressure can be produced with ACTH infusion at rates that produce plasma ACTH concentrations in the physiological range; (2) the rise in blood pressure occurs within 8 hours of ACTH infusion; (3) ACTH-induced hypertension is unlikely to be due to inhibition of /3-endorphin secretion. (Hypertension 7: 287-291, 1985) KEY WORDS • corticotropin • hypertension • /3-endorphin • corticosteroids T HE administration of adrenocorticotropic hormone (ACTH or corticotropin) to sheep has been shown to produce an adrenally dependent increase in blood pressure within 24 hours, which is associated with hypokalemia and hypernatremia.1 After an initial fall in sodium excretion for 24 to 48 hours, sodium excretion returned to preinfusion values. Urine volume and water intake were increased. In these studies ACTH was injected intramuscularly (Synacthen depot, Ciba-Geigy, Basel, Switzerland) or infused intravenously (Synacthen, Ciba-Geigy) at 20 /xg/kg/day, a rate that has been shown to produce maximal adrenocortical steroid output. 2The aim of the present study was to investigate the threshold and dose-response relationships for the effects of ACTH on blood pressure and ot...

Effects of direct renal arterial infusion of bufalin and ouabain in conscious sheep

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Cardiovascular Actions of Human Endothelin in Conscious Sheep

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