Evidence that prenatal steroid exposure produces oxidative stress in the kidney in male sheep

Prenatal glucocorticoid administration reduces renal function in adult offspring. But little is known about the effect of prenatal steroid exposure on oxidative stress in kidney. The objective of this study was to assess responses of a marker for oxidative stress in the kidney to infusion of angiotensin (ANG) peptides in adult male sheep exposed to steroid prenatally. 1–1.5 year old rams exposed to either Betamethasone (B) (n=6) or Vehicle (V) (n=6) at 80–81 days gestation were given intra renal ANG II or ANG 1–7 infusions(1 ng/kg/min) either alone or with an AT 1 R blocker (Candesartan; 0.3 mg/kg), AT 2 R blocker (PD 123319 10ng/kg/min) or Mas receptor blocker (D‐Alaangiotensin 1–7, D‐ALA, 10ng/kg/min) for 3 hours. Urinary 8‐isoprostane(8‐PGF) excretion was measured by EIA kit. ANOVA was used for data analysis. ANG II increased 8‐PGF excretion in B (from1.9±0.1 to 2.8±0.5ng/kg/h) but not in V sheep(p<0.05,F=6.1). Candesartan blocked the response to Ang II but PD didn't. ANG 1–7 infusion decreased the excretion of 8‐PGF in both groups (P<0.05,F=6.6). This response was blocked by D‐ALA. The results suggest that prenatal B exposure promotes an oxidative stress response in kidney. Blockade of the response by candesartan but not by PD suggests that the increased 8‐PGF excretion is mediated through AT 1 R activation. The decreased 8‐PGF excretion during ANG 1–7 infusion indicates ANG 1–7 might attenuate oxidative damage in B sheep. Supported by HD‐47584 and HD‐17644