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Impact of Antenatal Betamethasone (B) on p47 phox in Kidney and 8‐isoprostane Responses to Angiotensin II in Proximal Tubule Cells in Male Sheep after Uninephrectomy
Author(s) -
Bi Jianli,
Su Yixin,
Figueroa Jorge,
Chappell Mark C.,
Rose James C.
Publication year - 2012
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.26.1_supplement.1101.10
Subject(s) - kidney , medicine , endocrinology , nephron , betamethasone , offspring , angiotensin ii , oxidative stress , biology , pregnancy , receptor , genetics
Antenatal B administration reduces nephron number and causes hypertension in offspring. It is not clear if antenatal B enhances responses to a second insult (additional loss of nephrons). This study examined if antenatal betamethasone exposure increases susceptibility to a second “hit”. Adult male sheep exposed to B or Vehicle (V) (n=3–6) before birth underwent uninephrectomy (UN). Necropsy was performed 15 days after UN. Renal cortex was collected at both times. PTCs from both kidneys were stimulated with Ang II with or without its antagonists. P47 expression was determined by western blotting and 8‐PGF in media was measured by ELISA. Data were analyzed by ANOVA or T‐test. B exposure increased p47 expression (p<0.05) in kidneys obtained at uninephrectomy (first kidney) and at necropsy (second kidney) (B sheep vs. V sheep F=16, P=0.007). UN increased p47 in the second kidney in both groups (F=6.5, p=0.043). The highest expression of p47 was in the second kidney from the B exposed animals. Ang II stimulated 8‐PGF secretion from PTCs of the kidneys from B exposed sheep only (F=8.4, P=0.009 first kidney) and (F=5.5, P=0.044 second kidney). The response was blocked by candesartan but not PD123319. Ang II increased 8‐PGF secretion the most in PTCs from second kidney of B exposed animals (p<0.05). This suggests antenatal B exposure predisposes the kidney to oxidative stress from a“second hit”. Supported by HD‐47584 and HD‐17644