Osmolar regulation of endothelin-1 production by rat inner medullary collecting duct.
Recent evidence has implicated endothelin-1 (ET-1) as an autocrine inhibitor of inner medullary collecting duct (IMCD) sodium and water transport. The regulators of IMCD ET-1 production are, however, largely unknown. Because of the unique hypertonic environment of the IMCD, the effect of varying extracellular tonicity on IMCD ET-1 production was evaluated. Increasing media osmolality from 300 to 450 mosmol with NaCl or mannitol but not urea caused a marked dose- and time-dependent reduction in ET-1 release by and ET-1 mRNA in cultured rat IMCD cells. In contrast, increasing osmolality had no effect on ET-1 production by rat endothelial or mesangial cells. To see if ET-1 varies in a similar manner in vivo, ET-1 production was assessed in volume expanded (lower medullary tonicity) or volume depleted (high medullary tonicity) rats. Urinary ET-1 excretion and inner medulla ET-1 mRNA were significantly reduced in volume depleted as compared to volume expanded animals. These results indicate that extracellular sodium concentration inhibits ET-1 production specifically in IMCD cells. We speculate that extracellular sodium concentration, via regulation of ET-1 production, provides a link between volume status and IMCD sodium and water reabsorption.
Kohan
D E
DE
Department of Internal Medicine, Veterans Administration Medical Center, Salt Lake City, Utah 84132.
Padilla
E
E
D000199:Actins / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D003681:Dehydration / Q000503:physiopathology; D016232:Endothelins / Q000096:biosynthesis* / Q000235:genetics; D007679:Kidney Medulla / Q000187:drug effects / Q000502:physiology*; D007685:Kidney Tubules, Collecting / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008353:Mannitol / Q000494:pharmacology; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D009994:Osmolar Concentration; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012965:Sodium Chloride / Q000494:pharmacology; D014508:Urea / Q000494:pharmacology
D000199:Actins; D016232:Endothelins; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D008353:Mannitol; D012965:Sodium Chloride; D014508:Urea