Angiotensin I conversion to angiotensin II stimulates cortical collecting duct sodium transport.
Angiotensin (Ang) II directly stimulates epithelial sodium channel activity in the rabbit cortical collecting duct. Because Ang I and converting enzyme analogues might be present in the distal nephron, this raises the possibility of intraluminal generation of Ang II. Conversion of Ang I to Ang II was monitored by Ang II-dependent changes in intracellular sodium concentration as a reflection of sodium transport across the apical membrane. This involved imaging-based fluorescence microscopy with sodium-binding benzofuran isophthalate in isolated, perfused, cortical collecting-duct segments from rabbit kidney. Principal and intercalated cells were differentiated by rhodamine-conjugated peanut lectin. Control principal cell intracellular sodium concentration, during perfusion with 25 mmol/L NaCl and zero sodium in the bath plus monensin (10(-5) mol/L) averaged 5.8+/-0.14 mmol/L (n=156). The increase in intracellular sodium concentration, when luminal NaCl was increased from 25 to 150 mmol/L, was elevated by 3.5-fold in the presence of intraluminal Ang I (10(-6) mol/L). Also, the effects of Ang I on sodium transport were not significantly different from the effects of Ang II (10(-9) mol/L). Ang I was used in micromolar concentrations to ensure that there was sufficient substrate available for conversion to Ang II. Inhibition of the angiotensin-converting enzyme with captopril reduced the stimulatory effect of Ang I. These results suggest that intraluminal conversion of Ang I to Ang II can occur in the cortical collecting duct, resulting in enhanced apical sodium entry.
Komlosi
Peter
P
Department of Medicine, Division of Nephrology, University of Alabama at Birmingham, USA.
Fuson
Amanda L
AL
Fintha
Attila
A
Peti-Peterdi
János
J
Rosivall
Laszlo
L
Warnock
David G
DG
Bell
Phillip Darwin
PD
D000803:Angiotensin I / Q000378:metabolism* / Q000494:pharmacology; D000804:Angiotensin II / Q000378:metabolism* / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002216:Captopril / Q000494:pharmacology; D046508:Culture Techniques; D007685:Kidney Tubules, Collecting / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D007703:Peptidyl-Dipeptidase A / Q000032:analysis / Q000276:immunology; D011817:Rabbits; D012964:Sodium / Q000378:metabolism*
D000806:Angiotensin-Converting Enzyme Inhibitors; D000804:Angiotensin II; D000803:Angiotensin I; D002216:Captopril; D012964:Sodium; D007703:Peptidyl-Dipeptidase A