Background: Cushing syndrome causes hypertension and increased cardiovascular risk. The hypertensive mechanisms are not clearly defined. We hypothesized that glucocorticoid excess would induce salt-sensitivity, reflecting an impaired pressure-natriuresis response and abnormal salt handling by the kidney.
Methods: We modeled Cushing syndrome in male C57BL/6J mice with prolonged adrenocorticotropic hormone (ACTH) infusion and measured blood pressure on a 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.
Results: ACTH infusion increased blood pressure, induced nondipping and caused a transition to salt-sensitivity. ACTH infusion reduced the urine sodium/potassium ratio and abolished the diurnal rhythm of sodium excretion. In isolated renal artery, the response to nitric oxide was diminished, and at the mRNA level, we found evidence of arterial remodeling and enhanced TGF-β (transforming growth factor beta) signaling. Autoregulation of renal blood flow was impaired, as was the pressure-natriuresis response.
Conclusions: ACTH infusion impairs sodium excretion and causes a transition to nondipping and salt-sensitive blood pressure. 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.
Keywords: animals; blood pressure; diet; hypertension; kidney; renal circulation; sodium.