Effect of chronic ACTH infusion on blood pressure and kidney sodium excretion in male C56BL6J mice

Cushing Syndrome, reflecting endogenous overproduction of ACTH or exogenous exposure to glucocorticoid medication, increases cardiovascular risk. Hypertension is a major factor but underlying mechanisms are not clearly defined. We modelled Cushing Syndrome in male C57BL/6J mice with prolonged ACTH infusion and measured blood pressure on control diet and following high salt intake. In a separate group we assessed renal function and salt excretion, the in vivo pressure natriuresis response and ex vivo artery function. We found that ACTH infusion impairs sodium excretion and causes a transition to non-dipping and salt-sensitive BP. Renal hemodynamic and tubular abnormalities impair the pressure natriuresis response. Our findings provide a landscape of the complex physiological response to ACTH excess that may contribute to poor cardiovascular health in Cushing Syndrome.