Antenatal Betamethasone Causes Alterations in Angiotensin Receptors in Sheep Brain in a Gender Specific Manner

Abstract

We showed recently that antenatal betamethasone (Beta) exposure at mid gestation (80th day) elevates mean arterial pressure and attenuates baroreflex sensitivity in adult sheep of both sexes (1.8 yrs old). We now examined the effects of fetal Beta exposure on AT1, AT2, and Ang‐(1‐7) receptors in autonomic nuclei of the brain medulla in 1.8 yr old sheep using in vitro receptor autoradiography for binding with the non‐selective Ang receptor antagonist [125I‐Sar1‐Thr8]‐Ang II. Receptor subtypes were defined by competition with losartan for AT1, PD 123319 for AT2, [D‐Ala7]‐Ang‐(1‐7) for Ang‐(1‐7) in nucleus tractus solitarii (nTS), dorsal motor nucleus of vagus (dmnX) and area postrema (AP). There were no significant differences in overall binding density between Beta‐treated male or female sheep and their controls. There was a significant increase in the ratio of AT1 to A1‐7 receptors in Beta‐treated females, but not treated males, towards AT1 in nTS (0.7 ± 0.2 vs 3 ± 1), dmnX (0.6 ± 0.4 vs 4 ± 2) and AP (0.6 ± 0.2 vs 3 ± 1) versus the control group. In contrast, there was a 50‐60% reduction (p<0.03) in AT2 binding in dmnX and AP of Beta‐treated male sheep compared with controls. These sex‐specific changes in receptor subtypes are consistent with different mechanisms underlying the fetal programmed hypertension in male and female animals overall favoring a greater role for Ang II via the AT1 subtype. HD47584, HL51952