title: The effect of acute metabolic alkalosis on bicarbonate transport along the loop of Henle. The role of active transport processes and passive paracellular backflux.
abstract: 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)
authors.affiliation: 2nd University of Naples, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Capasso
authors.forename: R
authors.initials: R
authors.lastname: Unwin
authors.forename: F
authors.initials: F
authors.lastname: Ciani
authors.forename: G
authors.initials: G
authors.lastname: De Tommaso
authors.forename: M
authors.initials: M
authors.lastname: Vinciguerra
authors.forename: F
authors.initials: F
authors.lastname: Russo
authors.forename: N G
authors.initials: NG
authors.lastname: De Santo
mesh_terms: 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
chemical_list: 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