title: Antenatal betamethasone attenuates the angiotensin-(1-7)-Mas receptor-nitric oxide axis in isolated proximal tubule cells.
abstract: 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 angiotensin-(1-7) [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 percentage of basal uptake or area under the curve for Na+or percentage 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.
authors.affiliation: Department of Obstetrics and Gynecology, Wake Forest School of Medicine, Winston-Salem, North Carolina.
authors.forename: Yixin
authors.initials: Y
authors.lastname: Su
authors.affiliation: Department of Obstetrics and Gynecology, Wake Forest School of Medicine, Winston-Salem, North Carolina.
authors.forename: Jianli
authors.initials: J
authors.lastname: Bi
authors.affiliation: Department of Obstetrics and Gynecology, Wake Forest School of Medicine, Winston-Salem, North Carolina; vpulgar@wakehealth.edu.|Center of Research for Obstetrics and Gynecology, Wake Forest School of Medicine, Winston-Salem, North Carolina; and.|Hypertension and Vascular Research Center, Wake Forest School of Medicine, Winston-Salem, North Carolina.
authors.forename: Victor M
authors.identifier: 0000-0002-0049-9150
authors.initials: VM
authors.lastname: Pulgar
authors.affiliation: Hypertension and Vascular Research Center, Wake Forest School of Medicine, Winston-Salem, North Carolina.
authors.forename: Mark C
authors.initials: MC
authors.lastname: Chappell
authors.affiliation: Department of Obstetrics and Gynecology, Wake Forest School of Medicine, Winston-Salem, North Carolina.|Center of Research for Obstetrics and Gynecology, Wake Forest School of Medicine, Winston-Salem, North Carolina; and.
authors.forename: James C
authors.initials: JC
authors.lastname: Rose
mesh_terms: D000803:Angiotensin I / Q000378:metabolism*; D000818:Animals; D001623:Betamethasone / Q000494:pharmacology*; D001692:Biological Transport; D002478:Cells, Cultured; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology*; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism*; D010641:Phenotype; D061251:Primary Cell Culture; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D065608:Renal Reabsorption / Q000187:drug effects*; D012737:Sex Factors; D034561:Sheep, Domestic; D015398:Signal Transduction / Q000187:drug effects; D012964:Sodium / Q000378:metabolism*
chemical_list: D005938:Glucocorticoids; D010446:Peptide Fragments; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D043562:Receptors, G-Protein-Coupled; D009569:Nitric Oxide; D000803:Angiotensin I; D001623:Betamethasone; D012964:Sodium; C118790:angiotensin I (1-7)
keywords: fetal programming; kidney; renin-angiotensin system; sex differences