Rapid haemodynamic response to adrenocorticotrophin and the role of peripheral resistance in adrenocorticotrophin-induced hypertension in conscious sheep^*

Abstract

The haemodynamic effects associated with the onset of hypertension induced by infusion of adrenocorticotrophin (ACTH) were investigated in sheep. Analysis of haemodynamic data collected over 24 h by a computer-based monitoring system revealed that mean arterial pressure (MAP) was significantly increased after 4h. Cardiac output was significantly raised after 1h. The increased cardiac output was initially offset by a fall in calculated total peripheral resistance (CTPR) and MAP did not begin to rise until CTPR had returned to control values. This suggested that the return of CTPR to control values was essential for the development of hypertension. The development of ACTH-induced hypertension was prevented by both nisoldipine, a calcium channel blocker, and minoxidil, a vascular smooth muscle relaxant. Nisoldipine administration was also found to reverse established ACTH hypertension. A greater fall in MAP and CTPR occurred in the onset and established phase of ACTH hypertension sheep compared with normotensive controls. These results indicate that constriction of the peripheral vasculature is essential for the onset and maintenance of ACTH-induced hypertension in the sheep, and that the vasoconstriction does not involve a specific Ca^2±-dependent mechanism because minoxidil was as effective as nisoldipine in abolishing the pressor response to ACTH. The onset of ACTH-induced hypertension in sheep is characterized by very rapid haemodynamic changes with an increase in cardiac output and a relative increase in CTPR after an initial peripheral vasodilatation.