The effect of acute metabolic alkalosis on bicarbonate transport along the loop of Henle. The role of active transport processes and passive paracellular backflux.
The loop of Henle (LOH) reabsorbs approximately 15% of filtered HCO3- via a luminal Na(+)-H+ exchanger and H+ATPase. During acute metabolic alkalosis (AMA) induced by i.v. HCO3- infusion, we have observed previously inhibition of LOH net HCO3- reabsorption (JHCO3-), which contributes to urinary elimination of the HCO3- load and correction of the systemic alkalosis. To determine whether the activities of the Na(+)-H+ exchanger and/or H(+)-ATPase are reduced during AMA, two inhibitors believed to be sufficiently specific for each transporter were delivered by in vivo LOH microperfusion during AMA. AMA reduced LOH JHCO3- from 205.0 +/- 10.8 to 96.2 +/- 11.8 pmol.min-1 (P < 0.001). Luminal perfusion with bafilomycin A1 (10(-4) mol.l-1) caused a further reduction in JHCO3- by 83% and ethylisopropylamiloride (EIPA; 5.10(-4) mol.l-1) completely abolished net HCO3- reabsorption. The combination of bafilomycin A1 and EIPA in the luminal perfusate was additive, resulting in net HCO3- secretion (-66.6 +/- 20.8 pmol.min-1; P < 0.001) and abolished net fluid reabsorption (from 5.0 +/- 0.6 during AMA to 0.2 +/- 1.1 nl.min-1; P < 0.001). To establish whether HCO3- secretion via luminal stilbene-sensitive transport mechanism participates in LOH adaptation to AMA, we added diisothiocyanato-2,2'-stilbenedisulphonate (DIDS; 10(-4) mol.l-1) to the perfusate. No effect was found.(ABSTRACT TRUNCATED AT 250 WORDS)
Capasso
G
G
2nd University of Naples, Italy.
Unwin
R
R
Ciani
F
F
De Tommaso
G
G
Vinciguerra
M
M
Russo
F
F
De Santo
N G
NG
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D000208:Acute Disease; D000471:Alkalosis / Q000378:metabolism*; D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001639:Bicarbonates / Q000378:metabolism*; D001693:Biological Transport, Active / Q000187:drug effects / Q000502:physiology; D002245:Carbon Dioxide / Q000097:blood; D008138:Loop of Henle / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D018942:Macrolides; D008297:Male; D006180:Proton-Translocating ATPases / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D000889:Anti-Arrhythmia Agents; D000900:Anti-Bacterial Agents; D001639:Bicarbonates; D018942:Macrolides; D002245:Carbon Dioxide; D000584:Amiloride; C040929:bafilomycin A1; D006180:Proton-Translocating ATPases; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; C039614:ethylisopropylamiloride