Understanding the mechanism of adrenocortical steroid hypertension

Studies of the mechanism of ACTH induced hypertension in sheep have led to the hypothesis that adrenocortical steroids may raise blood pressure by a "hypertensinogenic" action which can be distinguished from effects mediated by occupancy of classical mineralocorticoid or glucocorticoid receptors. This concept is supported by recent structure-activity studies using synthetic and naturally occurring steroids. Development of steroid hypertension is rapid (4-6 h) and although associated with an increase in cardiac output, changes in total peripheral resistance are important. Many different mechanisms have been proposed to explain how steroids raise blood pressure. In sheep it has been shown that the autonomic nervous system and vasoactive prostanoids appear to buffer, rather than cause, the rise in blood pressure. The renin-angiotensin system, AVP and serotonin are also unlikely to be involved. Further, the effects of steroids on blood pressure are not simply related to effects on Na status and changes in body fluid volumes. A direct involvement of the central nervous system remains to be established. In understanding how ACTH raises blood pressure, studies in sheep have shown that it is important to try and dissociate the effects of steroids involved in development of hypertension from the many other actions of steroids.