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 intraaortically (1.4 pmol x kg(-1) x 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 x mm(-1) x 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 x mm(-1) x min(-1), P < 0.001) with less influence on H+ secretion. When indomethacin was infused (83 microg x kg(-1) x 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 x mm(-1) x min(-1), P < 0.02) and NaHCO3 (20.0 +/- 2.0 vs. 13.6 +/- 1.4 pmol x mm(-1) x 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.
Wesson
D E
DE
Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock 79430, USA.
Dolson
G M
GM
D000143:Acids / Q000378:metabolism*; D000284:Administration, Oral; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism; D019332:Endothelin-1 / Q000494:pharmacology*; D011464:Epoprostenol / Q000037:antagonists & inhibitors; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006859:Hydrogen / Q000378:metabolism; D007213:Indomethacin / Q000494:pharmacology; D007686:Kidney Tubules, Distal / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D011677:Punctures; D051381:Rats; D017208:Rats, Wistar; D017693:Sodium Bicarbonate / Q000494:pharmacology
D000143:Acids; D001639:Bicarbonates; D019332:Endothelin-1; D006859:Hydrogen; D017693:Sodium Bicarbonate; D011464:Epoprostenol; D007213:Indomethacin