Published online before print June 30, 2003, doi: 10.1161/01.HYP.0000081221.36703.01
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(Hypertension. 2003;42:195.)
© 2003 American Heart Association, Inc.
Scientific Contributions |
Angiotensin I Conversion to Angiotensin II Stimulates Cortical Collecting Duct Sodium Transport
From the Departments of Medicine and Physiology, Division of Nephrology, University of Alabama at Birmingham (P.K., A.L.F., A.F., J.P.-P., D.G.W., P.D.B.), and the Institute of Pathophysiology, Hungarian Academy of Sciences and Semmelweis University Nephrology Research Group (P.K., A.F., J.P.-P., L.R.), Budapest, Hungary.
Correspondence to Phillip Darwin Bell, 865 Sparks Center, 1720 Seventh Ave South, Birmingham, AL 35294. E-mail pdbell{at}uab.edu
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.
Key Words: angiotensin-converting enzyme • imaging • kallikrein • kidney • rabbits • renin-angiotensin system
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