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  • Title: Increased endothelin activity mediates augmented distal nephron acidification induced by dietary protein.
    Author: Khanna A, Simoni J, Hacker C, Duran MJ, Wesson DE.
    Journal: J Am Soc Nephrol; 2004 Sep; 15(9):2266-75. PubMed ID: 15339976.
    Abstract:
    The hypothesis that increased dietary protein augments distal nephron acidification and does so through an endothelin (ET-1)-dependent mechanism was tested. Munich-Wistar rats that ate minimum electrolyte diets of 50% (HiPro) and 20% (CON) casein-provided protein, the latter comparable to standard diet, were compared. HiPro versus CON had higher distal nephron net HCO(3) reabsorption by in vivo microperfusion (37.8 +/- 3.2 versus 16.6 +/- 1.5 pmol/mm per min; P < 0.001) as a result of higher H(+) secretion (41.3 +/- 4.0 versus 23.0 +/- 2.1 pmol/mm per min; P < 0.002) and lower HCO(3) secretion (-3.5 +/- 0.4 versus -6.4 +/- 0.8 pmol/mm per min; P < 0.001). Perfusion with H(+) inhibitors support that increased H(+) secretion was mediated by augmented Na(+)/H(+) exchange and H(+)-ATPase activity without augmented H(+),K(+)-ATPase activity. HiPro versus CON had higher levels of urine ET-1 excretion, renal cortical ET-1 addition to microdialysate in vivo, and renal cortical ET-1 mRNA, consistent with increased renal ET-1 production. Oral bosentan, an ET A/B receptor antagonist, decreased distal nephron net HCO(3) reabsorption (22.4 +/- 1.9 versus 37.8 +/- 3.2 pmol/mm per min; P < 0.001) as a result of lower H(+) secretion (28.4 +/- 2.4 versus 41.3 +/- 4.0 pmol/mm per min; P < 0.016) and higher HCO(3) secretion (-6.0 +/- 0.7 versus -3.5 +/- 0.4 pmol/mm per min; P < 0.006). The H(+) inhibitors had no additional effect in HiPro ingesting bosentan, supporting that ET mediated the increased distal nephron Na(+)/H(+) exchange and H(+)-ATPase activity in HiPro. Increased dietary protein augments distal nephron acidification that is mediated through an ET-sensitive increase in Na(+)/H(+) exchange and H(+)-ATPase activity.
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