Collecting duct–specific knockout of endothelin-1 causes hypertension and sodium retention

Aug 18, 2004The Journal of clinical investigation

Removing endothelin-1 in kidney water-filtering cells may cause high blood pressure and salt buildup

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Abstract

Mice lacking collecting duct-derived endothelin-1 (ET-1) exhibited significant hypertension on normal and high sodium diets.

  • Disruption of the ET-1 gene in the collecting duct resulted in no detectable CD ET-1 mRNA and reduced urinary ET-1 excretion.
  • Hypertension was observed in CD ET-1 KO mice on both normal and high sodium diets, suggesting a role for CD-derived ET-1 in blood pressure regulation.
  • Despite changes in blood pressure, body weight, sodium excretion, urinary aldosterone excretion, and plasma renin activity remained unchanged in CD ET-1 KO mice on a normal sodium diet.
  • On a high sodium diet, CD ET-1 KO mice experienced worsened hypertension, reduced urinary sodium excretion, and excessive weight gain.
  • Blood pressure was lowered in CD ET-1 KO mice treated with amiloride or furosemide, indicating potential therapeutic avenues for managing hypertension in these mice.

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