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

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 either 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-α), ER-beta (ER-β), 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 LPD1 offspring aortas there was a decrease in ER-α, ER-β, eNOS and an increase in AT₁-R protein expression and flutamide treatment increased ERβ, eNOS and decreased AT₁-R protein expression. In male LPD-2 offspring aortas, ER-β was increased with no changes in ER-α and eNOS proteins. Changes in vascular ER-mediated pathway may cause hypertension in female LPD offspring and flutamide treatment reverses this effect.