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Differential Expression of Renin‐Angiotensin System Components in the Choroid Plexus of Betamethasone Exposed and Control Sheep
Author(s) -
Marshall Allyson Catherine,
Shaltout Hossam A,
Pirro Nancy T,
Rose James C,
Diz Debra I,
Chappell Mark C
Publication year - 2013
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.27.1_supplement.1107.12
Subject(s) - renin–angiotensin system , endocrinology , offspring , medicine , betamethasone , angiotensin ii , choroid plexus , ventricle , blood pressure , chemistry , biology , pregnancy , central nervous system , genetics
The use of antenatal betamethasone (BM) is a widely accepted therapy to accelerate lung development and improve survival in preterm infants. We have developed an experimental model of programming whereby pregnant ewes are administered BM (2 doses of 0.17 mg/kg) or vehicle at the 80th day of gestation and offspring are delivered at term. Past studies show BM‐exposed (BMX) offspring develop elevated blood pressure and altered baroreflex sensitivity by 6‐months of age. In this study, we compared the synthesizing components of the renin‐angiotensin system (RAS) including renin, angiotensinogen, ACE, ACE2, and neprilysin (NEP) in the choroid plexus from the 4 th ventricle (ChP4) of male BMX and control offspring at 6‐months. No difference in the three peptidase activities was evident between BMX and control offspring; however, ACE2 activity was 3‐fold higher than either NEP or ACE. Moreover, all three enzymes were equally enriched ~2.5 fold in ChP4 brush border membranes (BBM) by Ca2+ precipitation. Both prorenin and active renin expression were detected in the ChP4; renin protein was significantly lower in the ChP4 of BMX animals (0.41 ± 0.03 vs 0.20 ± 0.03, p<0.05, N=4) and negatively correlated to Ang I‐intact angiotensinogen content (r = 0.78; p<0.01). We conclude that the ChP4 expresses all components of the RAS that would lead to local production of Ang II and Ang‐(1–7), although BMX may downregulate this system through the reduced expression of renin. HD47584