title: Antenatal betamethasone exposure alters renal responses to angiotensin-(1-7) in uninephrectomized adult male sheep.
abstract: Antenatal corticosteroid exposure reduces renal function and alters the intrarenal renin-angiotensin system to favor angiotensin activation of angiotensin type 1 receptor (AT1R) mediated responses in ovine offspring. This study aimed to assess whether antenatal steroid exposure would affect renal responses to the direct intrarenal infusion of angiotensin-(1-7) in rams and the angiotensin receptors involved in mediating responses to the peptide. Adult, uninephrectomized rams exposed to either betamethasone or vehicle before birth received intrarenal angiotensin-(1-7) infusions (1 ng/kg/min) alone or in combination with antagonists to angiotensin receptors for 3 h. Basal sodium excretion (UNa) was significantly lower and mean arterial pressure was significantly higher in betamethasone- compared to the vehicle-treated sheep. Angiotensin-(1-7) decreased UNa more in betamethasone- than in vehicle-treated sheep. Candesartan reversed the response to angiotensin-(1-7) but D-Ala(7)-angiotensin-(1-7) did not. Angiotensin-(1-7) infusion decreased effective renal plasma flow in both groups to a similar extent and the response was reversed by candesartan, but was not blocked by D-Ala(7)-angiotensin-(1-7). Glomerular filtration rate increased significantly in both groups after 3 h infusion of angiotensin-(1-7) plus candesartan. These results suggest that antenatal exposure to a clinically relevant dose of betamethasone impairs renal function in rams. Moreover, angiotensin-(1-7) appears capable of activating the AT1R in uninephrectomized rams.
authors.affiliation: 1Departments of Obstetrics and Gynecology, Wake Forest University School of Medicine, USA.
authors.forename: Jianli
authors.initials: J
authors.lastname: Bi
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Contag
authors.forename: Luke C
authors.initials: LC
authors.lastname: Carey
authors.forename: Lijun
authors.initials: L
authors.lastname: Tang
authors.forename: Nancy K
authors.initials: NK
authors.lastname: Valego
authors.forename: Mark C
authors.initials: MC
authors.lastname: Chappell
authors.forename: James C
authors.initials: JC
authors.lastname: Rose
mesh_terms: D000375:Aging; D000803:Angiotensin I / Q000097:blood / Q000494:pharmacology*; D000818:Animals; D001623:Betamethasone / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007668:Kidney / Q000098:blood supply / Q000187:drug effects* / Q000503:physiopathology / Q000601:surgery*; D008297:Male; D009392:Nephrectomy; D009929:Organ Size / Q000187:drug effects; D010446:Peptide Fragments / Q000097:blood / Q000494:pharmacology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000097:blood / Q000503:physiopathology*; D012039:Regional Blood Flow / Q000187:drug effects; D012756:Sheep; D012964:Sodium / Q000378:metabolism
chemical_list: D010446:Peptide Fragments; D000803:Angiotensin I; D001623:Betamethasone; D012964:Sodium; C118790:angiotensin I (1-7)