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Intact Angiotensinogen Consists of Oxidized and Reduced Conformation in Rodent Plasma
Author(s) -
Satou Ryousuke,
Katsurada Akemi,
Miyata Kayoko,
Kobori Hiroyuki,
Navar L
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.812.6
Subject(s) - rodent , rodent model , plasma , chemistry , medicine , biophysics , biology , physics , ecology , quantum mechanics
The pleiotropic actions of the renin‐angiotensin system (RAS) depend on the availability of abundant amounts of angiotensinogen (AGT) which generates angiotensins. Thus, determination of the intact AGT (iAGT) levels is required to evaluate the available levels of renin substrate. A recent study identified two types of plasma iAGT conformation which are oxidized AGT (oxi‐AGT) and reduced AGT (red‐AGT) in a disulfide bond, and showed that oxi‐AGT has a higher affinity for renin than red‐AGT. Oxidative stress augments oxi‐AGT levels accompanied by elevated blood pressure, suggesting that oxi‐AGT and red‐AGT switch may also be a key factor in RAS associated diseases. Thus, we determined iAGT, oxi‐AGT and red‐AGT levels in rodent plasma. Rat and mouse blood were obtained by cardiac micropuncture, then immediately mixed with inhibitors including a renin inhibitor. Total AGT (tAGT) levels were measured by tAGT ELISA which detects both cleaved and iAGT. iAGT, red‐AGT and oxi‐AGT levels in the plasma samples were determined by other assays. tAGT levels in rat and mouse plasma were 2026.4 ± 235.0 and 1073.8 ± 103.5 ng/ml, respectively. iAGT levels were 51 ± 2.4% of tAGT in rat plasma and 22 ± 2.0% of tAGT in mouse plasma. The lower relative level of iAGT in mouse plasma reflects the greater plasma renin activity in mice than rats. The ratio of oxi‐AGT and red‐AGT were 76:24 (rat) and 91:9 (mouse). Plasma iAGT consists of oxi‐AGT and red‐AGT suggesting that oxidative stress levels can influence Ang I generation by the AGT conformation switch.Furthermore, the lower availability of plasma iAGT in mice than rats suggests that it may be a limiting factor in angiotensin formation.