Renal endosomes contain angiotensin peptides, converting enzyme, and AT(1A) receptors.

Published

Journal Article

Kidney cortex and proximal tubular angiotensin II (ANG II) levels are greater than can be explained on the basis of circulating ANG II, suggesting intrarenal compartmentalization of these peptides. One possible site of intracellular accumulation is the endosomes. In the present study, we tested for endosomal ANG I, ANG II, angiotensin type 1A receptor (AT(1A)), and angiotensin converting enzyme (ACE) activity and determined whether these levels are regulated by salt intake. Male Sprague-Dawley rats were fed chow containing either high or low dietary sodium for 10-14 days. Blood and kidneys were harvested and processed for measurement of plasma, kidney, and renal intermicrovillar cleft and endosomal angiotensin levels. Kidney ANG I averaged 179 +/- 20 fmol/g and ANG II averaged 258 +/- 36 fmol/g in rats fed a high-sodium diet and were significantly higher, averaging 347 +/- 58 fmol/g and 386 +/- 55 fmol/g, respectively, in rats fed a low-salt diet. Renal intermicrovillar clefts and endosomes contained ANG I and ANG II. Intermicrovillar cleft ANG I and ANG II levels averaged 8.4 +/- 2.6 and 74 +/- 26 fmol/mg, respectively, in rats fed a high-salt diet and 7.6 +/- 1.7 and 70 +/- 25 fmol/mg in rats fed a low-salt diet. Endosomal ANG I and ANG II levels averaged 12.3 +/- 4.4 and 43 +/- 19 fmol/mg, respectively, in rats fed a high-salt diet, and these levels were similar to those observed in rats fed a low-salt diet. Renal endosomes from rats fed a low-salt diet demonstrated significantly more AT(1A) receptor binding compared with rats fed a high-salt diet. ACE activity was detectable in renal intermicrovillar clefts and was 2.5-fold higher than the levels observed in renal endosomes. Acute enalaprilat treatment decreased ACE activity in renal intermicrovillar clefts by 90% and in renal endosomes by 84%. Likewise, intermicrovillar cleft and endosomal ANG II levels decreased by 61% and 52%, respectively, in enalaprilat-treated animals. These data demonstrate the presence of intact angiotensin peptides and ACE activity in renal intermicrovillar clefts and endosomes, indicating that intact angiotensin peptides are formed and/or trafficked through intracellular endosomal compartments and are dependent on ACE activity.

Full Text

Duke Authors

Cited Authors

  • Imig, JD; Navar, GL; Zou, LX; O'Reilly, KC; Allen, PL; Kaysen, JH; Hammond, TG; Navar, LG

Published Date

  • August 1999

Published In

Volume / Issue

  • 277 / 2

Start / End Page

  • F303 - F311

PubMed ID

  • 10444586

Pubmed Central ID

  • 10444586

International Standard Serial Number (ISSN)

  • 0002-9513

Digital Object Identifier (DOI)

  • 10.1152/ajprenal.1999.277.2.F303

Language

  • eng

Conference Location

  • United States