Prenatal steroid exposure attenuates the nitric oxide (NO) ‐ cyclic guanosine monophosphate (cGMP) to Ang‐(1‐7) in mature male sheep

Abstract

Prenatal steroid administration reduces the natriuretic response to combined NaCl load and Ang‐(1‐7) infusions in adult sheep. Data also suggest that NO release and cGMP generation are involved in the natriuretic effect of Ang1‐7. Therefore, we wished to determine if prenatal steroid exposure reduced the ability of Ang‐(1‐7) to stimulate nitrite/nitrate (NOx) and cGMP excretion in adult animals. Sixteen rams prenatally exposed either to a clinically relevant dose of Beta or to vehicle at 80–81 days of gestation were studied at 18 months. Glomerular filtration rate (GFR), Na, NOx and cGMP excretion rates were measured before and during the infusion. Data were analyzed by ANOVA. Ang‐(1‐7) infusion at 10 pm.kg−1.min−1, in conjunction with a Na load (0.0275 mEq/kg BW/min), increased NOx excretion from 45.6 ± 7.0 to 60.2 ± 9.0 nmol/h/kg BW (p=0.02) and cGMP excretion from 4.2 ± 0.7 to 5.6 ± 0.8 nmol/h/kg BW (p=0.03) in vehicle animals. No significant increase in excretion rates were found in Beta animals. Sodium excretion showed positive correlations with NOx (p<0.01) and cGMP (p<0.001) excretion. There were no significant changes in GFR or plasma Na, NOx and cGMP levels in either group. These data suggest that the attenuated NOx‐cGMP responses to Ang‐(1‐7) may explain, in part, the reduced natriuretic effect of the peptide in the mature males prenatally exposed to steroid. (Supported by HD47584, HD17644)