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. and causes a natriuresis and diuresis. 4 These renal actions of ET-1, however, clearly do not cause the same biological responses. For instance, ET-1-induced vasoconstriction reduces glomerular filtration rate, thereby reducing sodium and water excretion, 2 and ET-1 directly inhibits sodium and water reabsorption by the collecting duct. 5 -6 The reasons for this apparent lack of coordinate effects of ET-1 are unknown; however, it probably reflects the independent actions of locally produced ET-1. At least two such locally acting systems exist for ET-1 in the kidney. The first, that of endothelial cell-derived ET-1 modulation of vascular smooth muscle tone, may play a role in the pathogenesis

No abstract

No abstract

No abstract