Mas And AT1 Receptor Expression In Adult Sheep Dorsomedial Medulla

Abstract

Recent studies in sheep reveal a programming effect of betamethasone exposure at 80 days gestation such that male and female offspring exhibit elevated pressure and impaired baroreflex sensitivity (BRS) for control of heart rate. Endogenous angiotensin II (Ang II) acting through AT1 receptors attenuates BRS, whereas endogenous Ang‐(1–7) enhances BRS in 6‐week‐old sheep. To determine whether the mas receptor, which has been shown to mediate the actions of Ang‐(1–7) in other species, exists in sheep brain medulla, Western blot hybridizations were performed using membrane homogenates from dorsomedial medulla of 18‐month‐old sheep. To quantify, beta‐actin was used as a loading control for densitometry normalization. Males (n = 6) and females (n = 5) exhibit protein for both AT1 and mas receptors with bands at molecular weights of 50–60 kDa for AT1 and 40 kDa for mas. There were no significant sex or treatment effects observed for the AT1 receptor, however protein expression for the mas receptor was significantly lower in sheep exposed to betamethasone in utero vs control sheep (0.03 ± 0.02 vs 0.33 ± 0.10 relative density units, n = 4–6; p < 0.05). In conclusion, receptor proteins for both AT1 and mas are detected in sheep medulla, and shifts of the mas/AT1 protein ratio toward AT1 may serve as a biochemical substrate for impaired BRS observed in betamethasone‐exposed animals. Support: HD047584, HD017644, HL56973, HL51952.