The renal medullary endothelin system in control of sodium and water excretion and systemic blood pressure

Purpose of review: Endothelin-1 is a multifunctional peptide that is produced by the kidney and may regulate a variety of renal functions. This review discusses recent developments in understanding the role of the medullary endothelin-1 system in regulating renal salt and water excretion and systemic blood pressure. Recent findings: The renal medulla is the major site of endothelin-1 synthesis and receptor expression in the kidney. Endothelin-1 in vitro can inhibit sodium or water transport in the collecting duct and thick ascending limb through autocrine pathways. Endothelin-1 also can increase medullary blood flow. These effects of endothelin-1 are partially mediated by nitric oxide and cyclooxygenase metabolites which are produced by most medullary cells. Mice with collecting duct-specific knockout of the endothelin-1 gene have impaired sodium excretion in response to sodium loading and have hypertension which worsens with high salt intake. The mice also have heightened sensitivity to vasopressin and decreased ability to excrete an acute water load. Mice with collecting duct-specific endothelin A receptor knockout have normal blood pressure and sodium excretion, but have reduced vasopressin responsiveness. Medullary endothelin-1 content is reduced in many forms of experimental hypertension. Summary: Medullary endothelin-1 regulates renal sodium and water transport and medullary blood flow. In particular, the medullary collecting duct is important in this process, but the medullary endothelin system involves complex interactions, through autocrine and paracrine pathways, between most cell types in the region. Medullary endothelin-1 is fundamentally important in physiologic regulation of renal sodium and water excretion and maintenance of normal systemic blood pressure.