title: Inhibition of angiotensin-converting enzyme modulates structural and functional adaptation to loop diuretic-induced diuresis.
abstract: The roles of elevated cell sodium concentrations and the angiotensin-aldosterone system (AAS) in the structural and functional adaptation of the distal tubule and collecting duct system to a chronic increase of sodium delivery were examined using electron microprobe and quantitative morphologic/stereologic analyses. Studies were performed on rats given the loop diuretic torasemide acutely (20 min) or chronically (12 days), either alone or in combination with the angiotensin-converting enzyme (ACE) inhibitor, enalapril. In the sodium-absorbing cells of the distal tubule and cortical collecting duct-that is, in distal convoluted tubule (DCT), connecting tubule (CNT) and principal cells-an acute increase in sodium delivery caused a significant rise in intracellular sodium concentration and rubidium uptake, the latter an index of in vivo Na,K(Rb)-ATPase activity. The elevated cell sodium concentrations returned to, or close to, control values during chronic torasemide treatment. Intracellular rubidium concentrations, measured after a 30-second rubidium exposure, were not different from controls in DCT and CNT cells but were still higher in principal cells. Since, however, the distribution space for rubidium was significantly increased in chronic torasemide animals, rubidium uptake, and hence Na,K-ATPase activity, must have increased in proportion to cell volume in DCT and CNT cells, but more than proportionately in principal cells. When ACE was inhibited during chronic torasemide, the epithelial volume of DCT and cortical collecting duct (CCD) was increased mainly by lengthening and not, as was the case in rats given torasemide alone, by thickening of the tubule wall. Adaptation of the proximal tubule exclusively by lengthening was not affected by inhibition of the ACE. These data indicate that changes in cell ion composition may participate in initiating cell processes leading to adaptation of distal nephron segments to chronically increased salt delivery. Inhibition of the ACE reverses the torasemide-induced increase in apparent Na pump density in principal cells and seems to shift the relationship between hypertrophy and hyperplasia noted in DCT and CCD after chronic torasemide in favor of hyperplasia.
authors.affiliation: Department of Physiology, University of Munich, Germany.
authors.forename: F X
authors.initials: FX
authors.lastname: Beck
authors.forename: A
authors.initials: A
authors.lastname: Ohno
authors.forename: E
authors.initials: E
authors.lastname: Müller
authors.forename: T
authors.initials: T
authors.lastname: Seppi
authors.forename: W
authors.initials: W
authors.lastname: Pfaller
mesh_terms: D000450:Aldosterone / Q000502:physiology; D000758:Anesthesia; D000804:Angiotensin II / Q000502:physiology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001835:Body Weight; D003243:Consciousness; D004231:Diuresis / Q000187:drug effects; D004232:Diuretics / Q000494:pharmacology*; D004573:Electrolytes / Q000097:blood / Q000652:urine; D004656:Enalapril / Q000494:pharmacology*; D006400:Hematocrit; D007672:Kidney Cortex / Q000187:drug effects / Q000201:enzymology; D007677:Kidney Function Tests; D007684:Kidney Tubules / Q000187:drug effects / Q000201:enzymology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012413:Rubidium / Q000493:pharmacokinetics; D012964:Sodium / Q000378:metabolism / Q000494:pharmacology; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology*; D000077786:Torsemide; D014556:Urine; D014662:Vasoconstrictor Agents / Q000378:metabolism; D014882:Water-Electrolyte Balance
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D004232:Diuretics; D004573:Electrolytes; D013449:Sulfonamides; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D000450:Aldosterone; D004656:Enalapril; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D012413:Rubidium; D000077786:Torsemide