Open AccessChemical modifications of the vasoconstrictor peptide angiotensin II by nitrogen oxides (NO, HNO 2 , HOONO)
Author(s) -
Ducrocq Claire,
Dendane Maryvonne,
Laprévote Olivier,
Serani Laurent,
Das Bhupesh C.,
BouchemalChibani Nadia,
Doan BichThuy,
Gillet Brigitte,
Karim Abdelhak,
Carayon Alain,
Payen Didier
Publication year - 1998
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1046/j.1432-1327.1998.2530146.x
Subject(s) - peroxynitrite , chemistry , nitration , tyrosine , arginine , angiotensin ii , residue (chemistry) , nitric oxide , nitrotyrosine , peptide , nitrosation , amine gas treating , stereochemistry , biochemistry , amino acid , superoxide , organic chemistry , nitric oxide synthase , receptor , enzyme
Nitric oxide (NO) and angiotensin II are natural regulators of blood pressure. Under aerobic conditions, NO is transformed into its higher oxides (N 2 O 4 , NO 2 , NO/NO 2 or N 2 O 3 ) and oxoperoxonitrate (currently named peroxynitrite) by coupling with superoxide. Previous studies have shown that these reactive nitrogen species should be involved in vivo in the transformation of cysteine and tyrosine into the corresponding nitrosothiol and 3‐nitrotyrosine. In the present study, attention has been focused on the relative reactivities of HNO 2 , peroxynitrite, and NO in the presence of dioxygen, towards the arginine and tyrosine residues of the peptide angiotensin II. Nitration of the tyrosine residue is clearly the main reaction with peroxynitrite. By contrast, besides 20 % of nitration of the tyrosine residue, NO in the presence of dioxygen leads to nitrosation reactions with the arginine residue similar to those observed with HNO 2 at pH 5, possibly through the intermediate N 2 O 3 reactive species. Angiotensin II is converted for the most part to peptides having lost either a terminal amine function or the whole guanido group, leading respectively to citrulline‐containing angiotensin II or to a diene derivative. Identification established mainly by tandem mass spectrometry of peptidic by‐products allows us to propose a cascade of nitrosations of all the amine functions of the arginine residue. Further in vivo studies show that transformations of the arginine residue in angiotensin II do not alter its vasoconstrictive properties, whereas nitration of the tyrosine residue totally inhibits them.