title: Mass-spectrometric identification of a novel angiotensin peptide in human plasma.
abstract: OBJECTIVE
  Angiotensin peptides play a central role in cardiovascular physiology and pathology. Among these peptides, angiotensin II (Ang II) has been investigated most intensively. However, further angiotensin peptides such as Ang 1-7, Ang III, and Ang IV also contribute to vascular regulation, and may elicit additional, different, or even opposite effects to Ang II. Here, we describe a novel Ang II-related, strong vasoconstrictive substance in plasma from healthy humans and end-stage renal failure patients.
  
  
  RESULTS
  Chromatographic purification and structural analysis by matrix-assisted laser desorption/ionisation time-of-flight/time-of-flight (MALDI-TOF/TOF) revealed an angiotensin octapeptide with the sequence Ala-Arg-Val-Tyr-Ile-His-Pro-Phe, which differs from Ang II in Ala1 instead of Asp1. Des[Asp1]-[Ala1]-Ang II, in the following named Angiotensin A (Ang A), is most likely generated enzymatically. In the presence of mononuclear leukocytes, Ang II is converted to Ang A by decarboxylation of Asp1. Ang A has the same affinity to the AT1 receptor as Ang II, but a higher affinity to the AT2 receptor. In the isolated perfused rat kidney, Ang A revealed a smaller vasoconstrictive effect than Ang II, which was not modified in the presence of the AT2 receptor antagonist PD 123319, suggesting a lower intrinsic activity at the AT1 receptor. Ang II and Ang A concentrations in plasma of healthy subjects and end-stage renal failure patients were determined by matrix-assisted laser desorption/ionisation mass-analysis, because conventional enzyme immunoassay for Ang II quantification did not distinguish between Ang II and Ang A. In healthy subjects, Ang A concentrations were less than 20% of the Ang II concentrations, but the ratio Ang A/Ang II was higher in end-stage renal failure patients.
  
  
  CONCLUSIONS
  Ang A is a novel human strong vasoconstrictive angiotensin-derived peptide, most likely generated by enzymatic transformation through mononuclear leukocyte-derived aspartate decarboxylase. Plasma Ang A concentration is increased in end-stage renal failure. Because of its stronger agonism at the AT2 receptor, Ang A may modulate the harmful effects of Ang II.
authors.affiliation: Charité Universitätsmedizin Berlin, Campus Benjamin Franklin Med Klinik IV, Hindenburgdamm 30, 12200 Berlin, Germany. Joachim.Jankowski@charite.de
authors.forename: Vera
authors.initials: V
authors.lastname: Jankowski
authors.forename: Raymond
authors.initials: R
authors.lastname: Vanholder
authors.forename: Markus
authors.initials: M
authors.lastname: van der Giet
authors.forename: Markus
authors.initials: M
authors.lastname: Tölle
authors.forename: Sevil
authors.initials: S
authors.lastname: Karadogan
authors.forename: Johan
authors.initials: J
authors.lastname: Gobom
authors.forename: Jens
authors.initials: J
authors.lastname: Furkert
authors.forename: Alexander
authors.initials: A
authors.lastname: Oksche
authors.forename: Eberhard
authors.initials: E
authors.lastname: Krause
authors.forename: Thi Nguyet Anh
authors.initials: TN
authors.lastname: Tran
authors.forename: Martin
authors.initials: M
authors.lastname: Tepel
authors.forename: Mirjam
authors.initials: M
authors.lastname: Schuchardt
authors.forename: Hartmut
authors.initials: H
authors.lastname: Schlüter
authors.forename: Annette
authors.initials: A
authors.lastname: Wiedon
authors.forename: Michael
authors.initials: M
authors.lastname: Beyermann
authors.forename: Michael
authors.initials: M
authors.lastname: Bader
authors.forename: Mihail
authors.initials: M
authors.lastname: Todiras
authors.forename: Walter
authors.initials: W
authors.lastname: Zidek
authors.forename: Joachim
authors.initials: J
authors.lastname: Jankowski
mesh_terms: D000368:Aged; D000804:Angiotensin II / Q000097:blood / Q000502:physiology; D000809:Angiotensins / Q000097:blood* / Q000737:chemistry* / Q000502:physiology; D000818:Animals; D002320:Cardiovascular Physiological Phenomena; D002319:Cardiovascular System; D002460:Cell Line; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood / Q000503:physiopathology; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D018345:Mice, Knockout; D008875:Middle Aged; D051381:Rats; D044139:Receptor, Angiotensin, Type 2 / Q000502:physiology; D014661:Vasoconstriction / Q000502:physiology
chemical_list: D000809:Angiotensins; D044139:Receptor, Angiotensin, Type 2; C516880:angiotensin A; D000804:Angiotensin II