We previously reported a sex-specific effect of antenatal treatment with betamethasone (Beta) on sodium (Na+) excretion in adult sheep whereby treated males but not females had an attenuated natriuretic response to Ang-(1-7). The present study determined the Na+ uptake and nitric oxide (NO) response to low dose Ang-(1-7) (1 pM) in renal proximal tubule cells (RPTC) from adult male and female sheep antenatally exposed to Beta or vehicle. Data were expressed as % of basal uptake or area under the curve (AUC) for Na+ or % of control for NO. Male Beta RPTC exhibited greater Na+ uptake than male vehicle cells (433±28% vs. 330±26%; p<0.05); however, Beta exposure had no effect on Na+ uptake in the female cells (255±16% vs. 255±14%; p>0.05). Ang-(1-7) significantly inhibited Na+ uptake in RPTC from vehicle male (214±11%) and from both vehicle (190±14%) and Beta (209±11%) females, but failed to attenuate Na+ uptake in Beta male cells. Beta exposure also abolished stimulation of NO by Ang-(1-7) in male, but not female RPTC. Both the Na+ and NO responses to Ang-(1-7) were blocked by Mas receptor antagonist [D-Ala7]-Ang-(1-7). We conclude that the tubular Ang-(1-7)-Mas-NO pathway is attenuated in males and not females by antenatal Beta exposure. Moreover, since primary cultures of RPTC retain both the sex and Beta-induced phenotype of the adult kidney in vivo they appear to be an appropriate cell model to examine the effects of fetal programming on Na+ handling by the renal tubules.
- fetal programming
- renin angiotensin system
- sex differences
- Copyright © 2016, American Journal of Physiology-Renal Physiology