RT Journal Article
SR Electronic
T1 Increased Endothelin Activity Mediates Augmented Distal Nephron Acidification Induced by Dietary Protein
JF Journal of the American Society of Nephrology
JO J. Am. Soc. Nephrol.
FD American Society of Nephrology
SP 2266
OP 2275
DO 10.1097/01.ASN.0000138233.78329.4E
VO 15
IS 9
A1 Khanna, Apurv
A1 Simoni, Jan
A1 Hacker, Callenda
A1 Duran, Marie-Josée
A1 Wesson, Donald E.
YR 2004
UL http://jasn.asnjournals.org/content/15/9/2266.abstract
AB 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 HCO3 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 HCO3 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 HCO3 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 HCO3 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.