title: Role of intrarenal endothelin in the generation and maintenance of hypertension.
abstract: Alterations in the renal metabolism and/or actions of endothelin-1 (ET-1) may be involved in the pathogenesis and maintenance of essential and renal parenchymal hypertension. ET-1 has the potential to modify a broad range of renal functions involved in controlling systemic blood pressure. First, the kidney clears a large percentage of ET-1 from the blood; decreased renal ET-1 clearance may contribute to hypertension occurring in the setting of chronic renal failure. Second, ET-1 potently constricts the renal vasculature resulting in increased fluid retention and possibly contributing to glomerular sclerosis; enhanced renal vascular and glomerular ET-1 production and target cell actions may play a role in essential hypertension or hypertension accompanying chronic renal failure, cyclosporine administration, or erythropoietin therapy. Lastly, ET-1 is also an autocrine inhibitor of collecting duct sodium and water reabsorption; reduced nephron ET-1 production may result in fluid retention in essential hypertension. Determination of the true role that ET-1 plays in the pathogenesis of the varied forms of hypertension awaits the development of safe, potent, and specific endothelin antagonists.
authors.affiliation: Department of Veterans Affairs Medical Center, Salt Lake City, Utah, USA.
authors.forename: B A
authors.initials: BA
authors.lastname: Markewitz
authors.forename: D E
authors.initials: DE
authors.lastname: Kohan
mesh_terms: D000818:Animals; D016232:Endothelins / Q000037:antagonists & inhibitors / Q000502:physiology*; D006801:Humans; D006973:Hypertension / Q000209:etiology*; D007676:Kidney Failure, Chronic / Q000209:etiology
chemical_list: D016232:Endothelins