Collecting duct-specific knockout of the endothelin B receptor causes hypertension and sodium retention.
Collecting duct (CD)-derived endothelin-1 (ET-1) inhibits renal Na reabsorption and its deficiency increases blood pressure (BP). The role of CD endothelin B (ETB) receptors in mediating these effects is unknown. CD-specific knockout of the ETB receptor was achieved using an aquaporin-2 promoter-Cre recombinase transgene and the loxP-flanked ETB receptor gene (CD ETB KO). Systolic BP in mice with CD-specific knockout of the ETB receptor, ETA receptor (CD ETA KO) and ET-1 (CD ET-1 KO), and their respective controls were compared during normal- and high-salt diet. On a normal-sodium diet, CD ETB KO mice had elevated BP, which increased further during high salt feeding. However, the degree of hypertension in CD ETB KO mice and the further increase in BP during salt feeding were lower than that of CD ET-1 KO mice, whereas CD ETA KO mice were normotensive. CD ETB KO mice had impaired sodium excretion following acute sodium loading. Aldosterone and plasma renin activity were decreased in CD ETB KO mice on normal- and high-sodium diets, while plasma and urinary ET-1 levels did not differ from controls. In conclusion, the CD ETB receptor partially mediates the antihypertensive and natriuretic effects of ET-1. CD ETA and ETB receptors do not fully account for the antihypertensive and natriuretic effects of CD-derived ET-1, suggesting paracrine effects of this peptide.
Ge
Yuqiang
Y
Division of Nephrology, University of Utah Health Sciences Center, 1900 East, 30 North, Salt Lake City, UT 84132, USA.
Bagnall
Alan
A
Stricklett
Peter K
PK
Strait
Kevin
K
Webb
David J
DJ
Kotelevtsev
Yuri
Y
Kohan
Donald E
DE
D000450:Aldosterone / Q000097:blood; D000821:Animal Feed; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D019332:Endothelin-1 / Q000378:metabolism; D006977:Hypertension, Renal / Q000378:metabolism / Q000503:physiopathology*; D007685:Kidney Tubules, Collecting / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009318:Natriuresis / Q000502:physiology; D019899:Paracrine Communication / Q000502:physiology; D044023:Receptor, Endothelin B / Q000235:genetics* / Q000378:metabolism*; D012083:Renin / Q000097:blood; D017673:Sodium Chloride, Dietary / Q000493:pharmacokinetics* / Q000652:urine
D019332:Endothelin-1; D044023:Receptor, Endothelin B; D017673:Sodium Chloride, Dietary; D000450:Aldosterone; D012083:Renin