Role of the renin-angiotensin-aldosterone system in collecting duct-derived endothelin-1 regulation of blood pressure.
Renal collecting duct (CD)-specific knockout of endothelin-1 (ET-1) causes hypertension and impaired Na excretion. A previous study noted failure to suppress the renin-angiotensin-aldosterone axis in these knockout (KO) mice, hence the current investigation was undertaken to examine the role of this system in CD ET-1 KO. Renal renin content was similar in kidneys from CD ET-1 KO and control mice during normal Na intake; high-Na intake suppressed renal renin content to a similar degree in KO and control. Plasma renin concentrations paralleled changes in renal renin content. Valsartan, an angiotensin receptor blocker (ARB), abolished the hypertension in CD ET-1 KO mice during normal Na intake. High-Na intake + ARB treatment increased blood pressure in CD ET-1 KO, but not in controls. High-Na intake was associated with reduced Na excretion in CD ET-1 KO animals, but no changes in water excretion or creatinine clearance were noted. Spironolactone, an aldosterone antagonist, also normalized blood pressure in CD ET-1 KO mice during normal Na intake, whereas high-Na intake + spironolactone raised blood pressure only in CD ET-1 KO animals. In summary, hypertension in CD ET-1 KO is partly due to angiotensin II and aldosterone. We speculate that CD-derived ET-1 may regulate, via a novel pathway, renal renin production.
Ge
Yuqiang
Y
Division of Nephrology, University of Utah Health Sciences Center, 1900 East 30 North, Salt Lake City, UT 84132, USA.
Huang
Yufeng
Y
Kohan
Donald E
DE
D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D001483:Base Sequence; D001794:Blood Pressure / Q000502:physiology*; D017931:DNA Primers / Q000235:genetics; D019332:Endothelin-1 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D005260:Female; D006973:Hypertension / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D007685:Kidney Tubules, Collecting / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology; D012083:Renin / Q000096:biosynthesis; D012084:Renin-Angiotensin System / Q000502:physiology*; D013148:Spironolactone / Q000494:pharmacology; D013777:Tetrazoles / Q000494:pharmacology; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology; D000068756:Valsartan
D047228:Angiotensin II Type 1 Receptor Blockers; D017931:DNA Primers; D019332:Endothelin-1; D000451:Mineralocorticoid Receptor Antagonists; D013777:Tetrazoles; D013148:Spironolactone; D000068756:Valsartan; D012083:Renin; D014633:Valine