Department of Obstetrics and Gynecology, and Center of Research for Obstetrics and Gynecology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
Am J Physiol Renal Physiol. 2010 Apr;298(4):F847-56. doi: 10.1152/ajprenal.00497.2009. Epub 2010 Jan 13.
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.
产前皮质类固醇可能对肾脏发育有长期影响,但尚未明确界定。我们的目的是比较两组 1 岁雄性绵羊对肾内输注血管紧张素 II (ANG II)的反应:一组在出生前暴露于临床相关剂量的倍他米松,另一组未暴露。我们希望验证这样一个假设,即产前类固醇暴露会增强成年后对 ANG II 的肾脏反应。六对雄性绵羊接受单侧肾切除术和肾动脉导管放置。绵羊接受 ANG II 或 ANG II 输注 24 小时,同时阻断血管紧张素 1 型 (AT(1))或 2 型 (AT(2))受体。倍他米松暴露的绵羊的平均动脉血压基线高于对照组 (分别为 85.8 +/- 2.2 和 78.3 +/- 1.0 mmHg,P = 0.003)。肾内输注 ANG II 不会增加全身血压 (P >/= 0.05),但显著降低有效肾血浆流量并增加肾动脉阻力 (P < 0.05)。与对照组相比,倍他米松暴露的绵羊肾内输注 ANG II 引起的流量减少和阻力增加更为显著 (倍他米松 P < 0.05,对照组 P >/= 0.05)。这种效应似乎是通过增加倍他米松暴露绵羊对 AT(1)受体的敏感性介导的。在 ANG II 输注期间,两组的钠排泄最初都减少;然而,在 24 小时后观察到反弹。在两组中,AT(1) 阻断后 24 小时均出现显著反弹。与倍他米松暴露组相比,AT(2) 阻断削弱了对照组的 24 小时反弹效应。总之,产前皮质类固醇暴露似乎通过增加 AT(1)和减少 AT(2)受体介导的作用来改变肾脏对 ANG II 的反应性,特别是与肾血流量和钠排泄有关。