title: Adrenal angiotensin: origin and site of generation.
abstract: BACKGROUND
  Circulating angiotensin (Ang) II accumulates in adrenal tissue via binding to Ang II type 1 (AT1) receptors, reaching levels that are 15 to 20 times higher than in blood. Adrenal tissue contains a second renin transcript that gives rise to a truncated prorenin representing a cytosolic form of renin. Here we investigated what percentage of adrenal Ang II originates at adrenal tissue sites, and whether intracellular renin contributes to adrenal angiotensin production.
  
  
  METHODS
  Concentrations of endogenous and iodine-125 (125I)-labeled Ang I and II were measured in adrenal tissue and blood from pigs after 125I-Ang I infusion.
  
  
  RESULTS
  In the adrenal tissue in all animals, 125I-Ang I was undetectable. In untreated pigs, adrenal 125I-Ang II was 17 +/- 1 times arterial 125I-Ang II, and tissue Ang I and II were 5 +/- 1 and 388 +/- 40 times higher than plasma Ang I and II. The AT1 receptor antagonist eprosartan reduced adrenal 125I-Ang II accumulation by 80%, and increased plasma Ang II to a greater degree than tissue Ang II. As a consequence, eprosartan equally reduced the tissue/plasma concentration ratios of both Ang II and 125I-Ang II. Captopril did not alter 125I-Ang II accumulation, and acutely, but not chronically, reduced the adrenal Ang II/I ratio.
  
  
  CONCLUSIONS
  More than 90% of adrenal Ang II originates at adrenal tissue sites. Local adrenal Ang II generation occurs extracellularly and is followed by internalization via AT1 receptor-mediated endocytosis. Enhanced angiotensin generation, combined with incomplete AT1 receptor blockade and the large adrenal AT1 receptor reserve, explains why eprosartan increased rather than decreased adrenal Ang II. Our data do not support angiotensin generation by truncated prorenin.
authors.affiliation: Department of Pharmacology, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Jorge P
authors.initials: JP
authors.lastname: van Kats
authors.forename: Wenxia
authors.initials: W
authors.lastname: Chai
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: Duncker
authors.forename: Maarten A D H
authors.initials: MA
authors.lastname: Schalekamp
authors.forename: A H Jan
authors.initials: AH
authors.lastname: Danser
mesh_terms: D000179:Acrylates / Q000494:pharmacology; D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism*; D000803:Angiotensin I / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D000804:Angiotensin II / Q000097:blood / Q000378:metabolism*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D002216:Captopril / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D005260:Female; D007093:Imidazoles / Q000494:pharmacology; D007261:Infusions, Intra-Arterial; D007457:Iodine Radioisotopes; D008297:Male; D008954:Models, Biological; D012084:Renin-Angiotensin System / Q000187:drug effects; D013552:Swine; D013876:Thiophenes / Q000494:pharmacology
chemical_list: D000179:Acrylates; D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D007093:Imidazoles; D007457:Iodine Radioisotopes; D013876:Thiophenes; D000804:Angiotensin II; C068373:eprosartan; D000803:Angiotensin I; D002216:Captopril