Early Rise In Blood Pressure Following Administration Of Adrenocorticotropic Hormone‐[1–24] In Humans

Abstract

1. An elevation in blood pressure has been consistently observed 24 h after adrenocorticotropic hormone (ACTH) administration and is caused by increased ACTH-stimulated cortisol secretion, in association with increased cardiac output. The aim of the present study was to investigate the previously undefined time of onset of this increase in blood pressure in normal humans. 2. Ten normal healthy volunteers received 250 mg ACTH-[1-24], in 500 mL normal saline, infused at a constant rate over 8 h. Six subjects also received a placebo infusion (normal saline only). Blood pressure, heart rate and cortisol levels were determined hourly. Adrenocorticotropic hormone (ACTH-[1-24] plus native ACTH) was measured at 0, 1, 7 and 8 h. 3. Infusion of ACTH-[1-24] produced maximal secretion rates of cortisol, resulting in a mean peak plasma level of 985 +/- 46 nmol/L at 8 h. In response, blood pressure and heart rate rose significantly by 2 h and remained generally elevated for the duration of the infusion. 4. The early onset of haemodynamic responses is consistent with classical steroid receptor-mediated genomic mechanisms, but could be due non-genomic mechanisms. 5. The cardiovascular consequences of therapeutic use of ACTH are well recognized. This results of the present study suggest that even diagnostic administration of ACTH, delivered over a few hours, may raise blood pressure.

Species Variability in Cardiovascular Research: The Example of Adrenocorticotrophin‐induced Hypertension

“…In our early studies of ACTH administration in humans (Synacthen Depot; Novartis Pharmaceuticals, North Ryde, NSW, Australia), we observed systolic blood pressure (SBP) increases in six of six normal healthy subjects and in five of six patients with essential hypertension, but not in two patients with Addison's disease on steroid replacement, indicating that the hypertension is adrenally dependent 9 . The magnitude of the rise in normal subjects was confirmed in subsequent studies 10 and, more recently, we showed acute increases in blood pressure in 10 normal subjects undergoing ACTH (Synacthen; Ciba‐Geigy, Basel, Switzerland) stimulation tests: blood pressure was elevated after 2 h of ACTH infusion 11 …”

Comparison of Bolus and Continuous Infusion of Adrenocorticotropic Hormone During Adrenal Vein Sampling

“…Another study investigated the effect of a continuous 5-day ACTH infusion (40U/24 h) on blood pressure in normotensive and hypertensive subjects also observed increased blood pressure after ACTH infusion (25). Jackson et al studied the effect of ACTH infusion on blood pressure and heart rate 1-8h after administration (26). Significant increases in blood pressure and heart rate were observed by 2h but not 1h, and remained generally elevated for the duration of the infusion in their study.…”

“…Previous studies have reported the effects of ACTH on blood pressure and heart rate (24)(25)(26)(27)(28). In the study conducted by Connell et al, they found that muscle injection of ACTH 0.5mg every 12h for five days markedly raised blood pressure in normal man (24).…”

Acute effects of hydrocortisone on plasma nitrate/nitrite activity and forearm vasodilator responsiveness in normal human subjects

“…In healthy humans, BP elevation is apparent within the first 24 h of exogenous cortisol administration [2][3][4] and adrenocorticotrophic hormone (ACTH) infusion causes an elevation of BP within 2-8 h. 8 The rapid increase in BP following ACTH infusion suggests that cortisol may have acute non-genomic haemodynamic effects that mediate an increase in BP. 8 Acute cellular effects of the mineralocorticoid aldosterone have been demonstrated in human uterine and chorionic arteries 9 and acute endothelial dysfunction has been demonstrated in the human forearm circulation following intra-arterial infusion of aldosterone.…”

“…8 Acute cellular effects of the mineralocorticoid aldosterone have been demonstrated in human uterine and chorionic arteries 9 and acute endothelial dysfunction has been demonstrated in the human forearm circulation following intra-arterial infusion of aldosterone. 10 Cortisol has rapid intracellular effects in vascular tissue in the setting of 11 ␤ -hydroxysteroid dehydrogenase (11 ␤ -HSD) inhibition; 9 however, no effects of cortisol on basal vascular tone have been demonstrated during short-term intra-arterial infusion.…”