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Fetal Betamethasone Exposure and Age Influence the Expression of AT7/mas Receptors in the Solitary Tract Nucleus
Author(s) -
Marshall Allyson Catherine,
Shaltout Hossam A,
Nautiyal Manisha,
Chappell Mark C,
Diz Debra I
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.1101.12
Subject(s) - betamethasone , endocrinology , medicine , baroreflex , receptor , fetus , solitary tract , medulla , in utero , angiotensin ii , renin–angiotensin system , biology , blood pressure , chemistry , pregnancy , heart rate , genetics
Betamethasone (BM) is given to women entering into early preterm labor to decrease infant mortality; however, fetal steroid exposure may lead to elevated mean arterial pressure (MAP) in adolescence. We show elevated MAP and decreased baroreflex sensitivity (BRS) at 6 and 20 months (mo) in sheep exposed in utero to BM is associated with alterations in the renin‐angiotensin system favoring a higher ratio of Ang II to Ang‐(1–7). An attenuated BRS is present at 6 wks, prior to increased MAP, and is associated with lower Ang‐(1–7) tone in the dorsal medulla; Ang‐(1–7) through the mas receptor opposes the actions of Ang II on BRS in this region. To establish whether altered mas receptor in the brain medulla contributes to the loss of Ang‐(1–7) tone, we determined the mas receptor protein expression by Western blot analysis in fetal, 6‐, and 20‐mo sheep. No difference between BM‐exposed and control sheep was evident at the fetal or 6‐mo time points. In contrast, mas receptor expression was significantly lower in 20‐mo BM (0.8 ± 0.13) than in control (1.8 ± 0.28) animals. Immunocytochemical data confirms these findings. While BM‐exposed sheep exhibit functional evidence of lower Ang‐(1–7) tone as early as 6 wks of age, the mechanisms may be age‐dependent with lower mas protein in older sheep suggested as a mechanism for the reduced BRS. Support: HD‐047584, HD‐017644, WFSM Venture Fund, Lois Groskert Heart Fund