Alterations in renal endothelin-1 production in the spontaneously hypertensive rat.
Endothelin-1 inhibits sodium and water transport systems in the inner medullary collecting duct. Endothelin-1 levels are reduced in the medulla of spontaneously hypertensive rats (SHR), raising the possibility that decreased inner medullary collecting duct production of endothelin-1 could contribute to inappropriate sodium and water retention. In the current study, immunoreactive endothelin-1 was measured in the urine, blood, and eluates from cortex and outer and inner medulla of SHR before (age 3-4 weeks) and after (age 8-9 weeks) the development of hypertension and in age-matched Wistar-Kyoto (WKY) controls. There was no difference in endothelin-1 levels between prehypertensive SHR and WKY rats. In contrast, 8-9-week-old SHR had significantly reduced endothelin-1 in the urine and outer and inner medulla, but not in the cortex or serum compared with those of WKY controls. Furthermore, inner medullary collecting duct cells from 8-9-week-old SHR, either acutely isolated or cultured, released less endothelin-1 than did those from WKY rats. Finally, the level of endothelin-1 messenger RNA was only reduced in the inner medulla and in inner medullary collecting duct cells from 8-9-week-old SHR. In summary, renal medullary, and in particular terminal collecting duct, endothelin-1 production is reduced in SHR only after the development of hypertension. Such decreases in inner medullary collecting duct endothelin-1 production may contribute to the hypertensive state in SHR.
Hughes
A K
AK
Division of Nephrology, Veterans Administration Medical Center, Salt Lake City, Utah 84132.
Cline
R C
RC
Kohan
D E
DE
D000199:Actins / Q000235:genetics; D000818:Animals; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D016232:Endothelins / Q000096:biosynthesis* / Q000235:genetics; D006973:Hypertension / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism*; D007679:Kidney Medulla; D007685:Kidney Tubules, Collecting / Q000166:cytology / Q000378:metabolism; D008297:Male; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014018:Tissue Distribution; D014158:Transcription, Genetic
D000199:Actins; D016232:Endothelins; D012333:RNA, Messenger; D004247:DNA