Identification of angiotensin-(1-7) in rat brain. Evidence for differential processing of angiotensin peptides.
Tissue and plasma forms of angiotensin (Ang) peptides were characterized by reverse-phase high performance liquid chromatography and three specific radioimmunoassays. This method allowed resolution of 10 Ang peptides and revealed distinctive distributions for the three principal Ang peptides in the brain, adrenal gland, and plasma. In extracts from the rat hypothalamus, approximately equimolar amounts of Ang-(1-7), Ang-II, and Ang-I were detected (1.10, 1.18, and 1.45 pmol/g of tissue, respectively). A similar profile was observed in the medulla oblongata and amygdala, although the content of these three peptides was 40-70% less than that seen in the hypothalamus. In the adrenal gland, the predominant peptide was Ang-II (1.07 pmol/g); levels of Ang-(1-7) (0.19 pmol/g) and Ang-I (0.14 pmol/g) were approximately 20% that of Ang-II. In plasma, the major angiotensin was Ang-I (0.13 pmol/ml), with lower levels of Ang-(1-7) and Ang-II (0.01-0.02 pmol/ml). This study is the first demonstration of the endogenous presence of Ang-(1-7) in central and peripheral tissues of the rat. Moreover, the data suggest tissue-specific processing of angiotensins, with Ang-(1-7) being a predominant Ang peptide in the central nervous system. In light of the recent biological properties described for this peptide, Ang-(1-7) may represent an active member of Ang peptides in the brain.
Chappell
M C
MC
Department of Brain and Vascular Research, Cleveland Clinic Foundation, Ohio 44195-5070.
Brosnihan
K B
KB
Diz
D I
DI
Ferrario
C M
CM
D000311:Adrenal Glands / Q000032:analysis; D000803:Angiotensin I / Q000032:analysis; D000804:Angiotensin II / Q000032:analysis*; D000809:Angiotensins / Q000032:analysis / Q000235:genetics; D000818:Animals; D001923:Brain Chemistry; D002851:Chromatography, High Pressure Liquid; D007031:Hypothalamus / Q000032:analysis; D007106:Immune Sera; D008297:Male; D010446:Peptide Fragments / Q000032:analysis*; D011499:Protein Processing, Post-Translational; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains
D000809:Angiotensins; D007106:Immune Sera; D010446:Peptide Fragments; D000804:Angiotensin II; D000803:Angiotensin I; C118790:angiotensin I (1-7)