Contribution of Na+-H+ exchange to sodium reabsorption in the loop of henle: a microperfusion study in rats.
1. The contribution of apical Na+-H+ exchange to sodium reabsorption in the thick ascending limb of the loop of Henle (TALH) in vivo was examined in anaesthetized rats by perfusing loops of Henle of superficial nephrons with solutions containing the Na+-H+ exchange inhibitor, ethyl isopropyl amiloride (EIPA). 2. Using a standard perfusate, no statistically significant effect of EIPA on net sodium reabsorption (JNa) was detected. However, when sodium reabsorption in the pars recta of the proximal tubule was minimized by using a low-sodium perfusate, EIPA reduced JNa from 828 +/- 41 to 726 +/- 37 pmol min-1 (P < 0.05), indicating that apical Na+-H+ exchange can make a small contribution to net sodium reabsorption in the TALH in vivo. This contribution appears to be dependent on the bicarbonate load, since an increase in the latter led to an enhancement of EIPA-sensitive sodium transport. 3. Addition of the Na+-K+-2Cl- cotransport inhibitor, bumetanide, to the low-sodium perfusate reduced baseline JNa to 86 +/- 27 pmol min-1. In this setting, EIPA reduced JNa further, to -24 +/- 18 pmol min-1 (P < 0.05), an effect similar to that seen in the absence of bumetanide. This finding argues against previous suggestions (based on in vitro evidence) that inhibition of the Na+-K+-2Cl- cotransporter leads to an increase in apical Na+-H+ exchange in the TALH.
Shirley
D G
DG
Division of Biomedical Sciences, Imperial College School of Medicine, Charing Cross Hospital, London W6 8RF, UK. d.shirley@cxwms.ac.uk
Walter
S J
SJ
Unwin
R J
RJ
Giebisch
G
G
D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D000758:Anesthesia; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D001639:Bicarbonates / Q000494:pharmacology; D002034:Bumetanide / Q000494:pharmacology; D004232:Diuretics / Q000494:pharmacology; D005919:Glomerular Filtration Rate / Q000187:drug effects; D066298:In Vitro Techniques; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism; D008138:Loop of Henle / Q000378:metabolism*; D008297:Male; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000378:metabolism*; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism*
D000889:Anti-Arrhythmia Agents; D001639:Bicarbonates; D004232:Diuretics; D017923:Sodium-Hydrogen Exchangers; D002034:Bumetanide; D000584:Amiloride; D012964:Sodium; C039614:ethylisopropylamiloride