Developmental effect of antenatal exposure to betamethasone on renal angiotensin II activity in the young adult sheep

Abstract

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 (AT1) or type 2 (AT2) 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 AT1 receptor among betamethasone-exposed sheep. Sodium excretion initially decreased in both groups during ANG II infusion; however, a rebound was observed after 24 h. AT1 blockade was followed by a significant rebound after 24 h in both groups. AT2 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 AT1- and decreasing AT2 receptor-mediated actions particularly as related to renal blood flow and sodium excretion.