In Utero Low-Protein Diet Alters Vascular Estrogen Receptors,Endothelial Nitric Oxide Synthase and Angiotensin 11 Subtype 1 Receptors in adult male and female rat offspring

Order of Publishing in Issue: 
Volume :3
Issue :4
October, 2009 - December, 2009
Page No: 
Pandu R. R. Gangula [1], Luckey Reed [2] and Chandrasekhar Yallampalli [2]
[1] Department of Obstetrics and Gynecology, Meharry Medical College, Nashville, TN, USA
[2] Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, Texas, USA

Background/Aims: We investigated whether: 1) in utero low-protein diet (LPD) induced adult hypertension alters vascular estrogen receptor (ER)-related mechanism in both male and female vascular tissues; and whether 2) flutamide, a specific, non-steroidal competitive antagonist of the androgen receptor, improved this system in female offspring. Methods: Pregnant rats were fed eitherĀ  with 20% protein (control), or 6% protein (LPD) from day 1 (LPD-1) or day 12 (LPD-2) of
gestation. Male and female hypertensive offspring were treated when adult with flutamide (10 mg/day/kg body weight, subcutaneous) for four days. Aortas (vascular) were isolated from
control, LPD-1 female, LPD-2 male and flutamide treated female LPD-1 offspring. ERalpha (ER-?), ER-beta (ER-?), endothelial nitric oxide synthase (eNOS), and the angiotensin 11
subtype 1 receptor 1 (AT1-R) protein levels were analyzed using western immunoblotting.
Results and Conclusion: In female LPD- 1 offspring aortas there was a decrease in ER-?,
ER-?, eNOS and an increase in AT1-R protein expression and flutamide treatment increased ER-
?, eNOS and decreased AT1-R protein expression. In male LPD-2 offspring aortas, ER-? was
increased with no changes in ER-? and eNOS proteins. Changes in vascular ER-mediated
pathway may cause hypertension in female LPD offspring and flutamide treatment reverses this

Low-protein diet, estrogen receptors, nitric oxide, angiotensin receptor, flutamide.
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