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Estrogen receptor (ER)‐induced Angiotensin 1‐7 (Ang1‐7) protects against Ischemia/Reperfusion‐Induced Acute Kidney Injury (I/R‐AKI)
Author(s) -
LopezRuiz Arnaldo,
Soljancic Andrea,
Chandrashekar Kiran,
Juncos Ramiro,
Liu Ruisheng,
Reckelhoff Jane,
Juncos Luis A
Publication year - 2011
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.25.1_supplement.835.13
Subject(s) - acute kidney injury , estrogen receptor , medicine , estrogen , ischemia , angiotensin ii , reperfusion injury , receptor , cardiology , endocrinology , pharmacology , cancer , breast cancer
Ang1‐7, produced by ACE2, is a contraregulatory member of the renin angiotensin system that decreases renal injury. Because Ang1‐7 levels are higher in females, we tested whether estrogen‐induced Ang1‐7 contributes to the decreased susceptibility of females to I/R‐AKI. Male (M) and female (F) SD rats received either vehicle, fulvestrant (FVT: ER antagonist), A779 (Ang1‐7 antagonist) or both, and then subjected to 40 min of I/R‐AKI. At 72h we measured plasma Creatinine (Creat), urine Ang1‐7, and renal inflammation (TNFα), injury (urine NGAL) and ACE2 expression.Ang1‐7 ng/ml ACE2 ng/μg Creat mg/dl TNFα pg/μg uNGAL μg/mlM‐AKI 0.7±0.01 0.4±0.04 2.3±0.2 1.4±0.1 3.4±0.1 F‐AKI 1.1±0.1 * 0.9±0.2 * 1.7±0.1 * 1.0±0.03 * 3.1±0.1 * M‐AKI+FVT 0.6±0.02 * 0.5±0.01 2.4±0.05 1.3±0.05 3.3±0.1 F‐AKI+FVT 0.7±0.1 # 0.6±0.8 # 2.6±0.1 * # 1.6±0.2 * # 3.5±0.1 # M‐AKI+A779 0.7±0.2 0.5±0.04 * 2.8±0.3 * 2.2±0.02 * 3.9±0.1 * F‐AKI+A779 1.2±0.02 * 1.1±0.1 # 2.5±0.4 # 1.8±0.2 * 3.9±0.1 # M‐AKI+ FVT+A779 0.7±0.1 0.5±0.03 * 2.7±0.01 2.2 ±0.1 * 3.8±0.1 F‐AKI +FVT+A779 0.6±0.01 0.6±0.3 # 3.1±0.04 & 2.8±0.4 & 4.4±0.2 &p<0.05 * vs M‐AKI, # vs F‐AKI, & vs M‐AKI+FVT+A779F have higher Ang1‐7 and ACE2, and less susceptibility to I/R‐AKI than M. Blocking the ER reduces gender differences in all parameters, whereas blocking Ang1‐7 lessens the differences in renal injury, suggesting that ER activation increases Ang1‐7 thus protecting against AKI.