Developmental effect of antenatal exposure to betamethasone on renal angiotensin II activity in the young adult sheep.
Antenatal corticosteroids may have long-term effects on renal development which have not been clearly defined. Our objective was to compare the responses to intrarenal infusions of ANG II in two groups of year-old, male sheep: one group exposed to a clinically relevant dose of betamethasone before birth and one not exposed. We wished to test the hypothesis that antenatal steroid exposure would enhance renal responses to ANG II in adult life. Six pairs of male sheep underwent unilateral nephrectomy and renal artery catheter placement. The sheep were infused for 24 h with ANG II or with ANG II accompanied by blockade of the angiotensin type 1 (AT(1)) or type 2 (AT(2)) receptor. Baseline mean arterial blood pressure among betamethasone-exposed sheep was higher than in control animals (85.8 +/- 2.2 and 78.3 +/- 1.0 mmHg, respectively, P = 0.003). Intrarenal infusion of ANG II did not increase systemic blood pressure (P >/= 0.05) but significantly decreased effective renal plasma flow and increased renal artery resistance (P < 0.05). The decrease in flow and increase in resistance were significantly greater in betamethasone- compared with vehicle-exposed sheep (betamethasone P < 0.05, vehicle P >/= 0.05). This effect appeared to be mediated by a heightened sensitivity to the AT(1) receptor among betamethasone-exposed sheep. Sodium excretion initially decreased in both groups during ANG II infusion; however, a rebound was observed after 24 h. AT(1) blockade was followed by a significant rebound after 24 h in both groups. AT(2) blockade blunted the 24-h rebound effect among the vehicle-exposed sheep compared with the betamethasone-exposed sheep. In conclusion, antenatal corticosteroid exposure appears to modify renal responsiveness to ANG II by increasing AT(1)- and decreasing AT(2) receptor-mediated actions particularly as related to renal blood flow and sodium excretion.
Contag
Stephen A
SA
Department of Obstetrics and Gynecology, and Center of Research for Obstetrics and Gynecology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA. contag@live.com
Bi
Jianli
J
Chappell
Mark C
MC
Rose
James C
JC
D000804:Angiotensin II / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D057912:Angiotensin II Type 2 Receptor Blockers; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D001623:Betamethasone / Q000008:administration & dosage / Q000494:pharmacology*; D001713:Biphenyl Compounds; D001794:Blood Pressure / Q000187:drug effects; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D005938:Glucocorticoids / Q000008:administration & dosage / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology; D007261:Infusions, Intra-Arterial; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D008094:Lithium / Q000378:metabolism / Q000652:urine; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011725:Pyridines / Q000494:pharmacology; D011897:Random Allocation; D017597:Renal Blood Flow, Effective / Q000187:drug effects; D012756:Sheep; D012964:Sodium / Q000378:metabolism / Q000652:urine; D013777:Tetrazoles / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects
D047228:Angiotensin II Type 1 Receptor Blockers; D057912:Angiotensin II Type 2 Receptor Blockers; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D005938:Glucocorticoids; D007093:Imidazoles; D011725:Pyridines; D013777:Tetrazoles; D000804:Angiotensin II; C073402:PD 123319; D001623:Betamethasone; D008094:Lithium; D012964:Sodium; C081643:candesartan