Endothelin-1 increases rat distal tubule acidification in vivo.

Because endothelin receptor inhibition blunts increased distal tubule acidification induced by dietary acid, we examined whether endothelin-1 (ET-1) increases acidification of in vivo perfused distal tubules of anesthetized rats. ET-1 was infused intra-aortically (1.4 pmol ⋅ kg-1 ⋅ min-1) into control animals and into those with increased distal tubule HCO3 secretion induced by drinking 80 mM NaHCO3 solution for 7-10 days. ET-1 increased distal tubule acidification in both control and NaHCO3 animals. Increased acidification in control animals was mediated by increased distal tubule H+ secretion (23.7 ± 2.2 vs. 18.7 ± 1.7 pmol ⋅ mm-1 ⋅ min-1, P < 0.05) with no changes in HCO3 secretion. By contrast, ET-1 increased distal tubule acidification in NaHCO3 animals predominantly by decreasing HCO3 secretion (-9.5 ± 1.0 vs. -18.7 ± 1.8 pmol ⋅ mm-1 ⋅ min-1, P < 0.001) with less influence on H+ secretion. When indomethacin was infused (83 μg ⋅ kg-1 ⋅ min-1) to inhibit synthesis of prostacyclin, an agent previously shown to increase HCO3 secretion in the distal tubule, ET-1 increased distal tubule H+ secretion in both control (24.3 ± 2.2 vs. 15.7 ± 1.6 pmol ⋅ mm-1 ⋅ min-1, P < 0.02) and NaHCO3 (20.0 ± 2.0 vs. 13.6 ± 1.4 pmol ⋅ mm-1 ⋅ min-1, P < 0.05) without affecting HCO3 secretion. The data show that ET-1 increases distal tubule acidification in vivo and can do so by increasing H+ secretion and by decreasing HCO3 secretion when the latter is augmented by dietary NaHCO3.