Aldosterone signaling and soluble adenylyl cyclase—A nexus for the kidney and vascular endothelium

• Soluble adenylyl cyclase (sAC) is a mediator of aldosterone signaling.
• sAC affects renal salt and water homeostasis.
• sAC affects endothelial stiffness.
• Nuclear sAC regulates renal and endothelial gene expression.
• sAC is a potential therapeutic target in renal and cardiovascular disease.

The steroid hormone aldosterone regulates the reabsorption of water and ions in the kidney and plays a central role in blood pressure regulation and homeostasis. In recent years, the vascular endothelium has been established as an important aldosterone target organ with major implications in renal and cardiovascular health and disease. Different lines of evidence suggest that the calcium- and bicarbonate-activated soluble adenylyl cyclase (sAC) is a novel mediator of aldosterone signaling in both the kidney and vascular endothelium. This review summarizes our current understanding of the molecular mechanisms of sAC gene expression regulation in the kidney and vascular endothelium and outlines the potential clinical implications of sAC in chronic kidney disease and cardiovascular disease. This review is part of a special issue entitled: The role of soluble adenylyl cyclase in health and disease. This article is part of a Special Issue entitled: The role of soluble adenylyl cyclase in health and disease.