Abstract 1263: Collecting Duct Endothelin B Receptors Lower Blood Pressure and Increase Sodium Excretion
Introduction: Collecting duct (CD)-derived endothelin-1 (ET-1) inhibits renal Na reabsorption and reduces blood pressure (BP). The receptor mediating this effect is unknown.
Hypothesis: Autocrine activation of CD Endothelin B (ETB) by ET-1 results in sodium excretion and a reduction of BP.
Methods: CD-specifc ETB receptor knockout mice (CD ETB KO) were generated by intercross of mice featuring loxP sites flanking ETB coding regions (floxed ETB mice) and aquaporin-2-Cre transgenic mice (AQ2-Cre). BP of CD ETB KOs and AQ2-Cre negative floxed littermates was measured by telemetry during normal and high salt diet. Daily Na excretion and Na excretion following acute intra-peritoneal saline loading was assessed.
Results: BP was raised in CD ETB KO mice (132±3 mmHg vs. 119±1 mmHg) and increased further during high salt diet (139±3 vs. 119±2; p<0.01; n=6–12/group). However, the BP increase was less than previously reported in CD ET-1 KO mice. Urinary ET-1 was increased in both groups during salt feeding. CD ETB KO mice had lower plasma renin activity on normal (1.2±0.4 vs. 4.8±1.1 pg Al/μg/hr; p<0.001) and high (0.6 ±0.3 vs. 1.8±0.3; p<0.001) Na diets, and lower urinary aldosterone excretion on a normal Na diet, than controls, consistent with volume expansion in KO mice. Acute Na excretion in response to saline loading was impaired in CD ETB KO but daily Na excretion was unchanged.
Conclusions: CD-derived ET-1 inhibits acute Na excretion and lowers BP through autocrine activation of ETB. Additional paracrine effects of CD ET-1 that reduce BP may account for the greater BP increase observed following CD ET-1 KO, compared to CD ETB KO.