Comparison of ANG II in fetal and pregnant sheep: metabolic clearance and vascular sensitivity.

Comparison of ANG II in fetal and pregnant sheep: metabolic clearance and vascular sensitivity.
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胎羊和怀孕羊 ANG II 的比较:代谢清除率和血管敏感性。

DOI:
10.1152/ajpendo.1995.268.2.e237
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发表时间:
1995
期刊:
The American journal of physiology.
影响因子:
--
通讯作者:
Magness,RR
Magness,RR
中科院分区:
--
文献类型:
--
作者:
Rosenfeld,CR;Gresores,A;Roy,TA;Magness,RR

文献摘要

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胎羊对输注血管紧张素II(ANG II)的反应低于妊娠母羊。这可能反映了更高的胎儿代谢清除率(MCRANGII),从而降低血浆ANG II水平。因此,我们测定了胎儿MCRANGII、半衰期(T1/2)和ANG II的胎盘清除。胎羊(n = 13;妊娠113-139天)接受0.573-5.73微克ANG II/min静脉注射30分钟,同时监测动脉压和心率。在30分钟输注之前和期间获得系列血液样品以测量ANG II并计算MCRANGII,并且在停止输注之后获得系列血液样品以确定T1/2。MCRANGII在整个妊娠期和剂量≤ 2.29微克/分钟时相似(成人为683 +/- 49 vs. 74 +/- 5 ml.min-1.kg-1),但在5.73微克ANG II/分钟时低30-40%(494 +/- 57 ml.min-1.kg-1,P < 0.05)。T1/2为15-21 s。胎儿胎盘ANG II清除率平均为87 +/- 3,子宫胎盘清除率平均为20 +/- 6%;这不受剂量影响,与血浆ANG II水平呈线性关系,饱和度不明显。血浆ANG II水平随输注速率成比例升高,并不随时间发生显著变化;因此,胎儿血浆ANG II浓度可以从MCRANGII预测。在每个输注速率和时间点测量和预测的ANG II水平相似:r = 0.87,斜率= 0.87(P < 0.001)。在同等预测血浆ANG II水平下,胎儿和母体的升压反应相似(P > 0.1),然而,脐血管阻力的增加超过子宫胎盘血管阻力的增加(P < 0.03)。胎儿MCRANGII约为母体的10倍,部分反映了胎盘循环清除ANG II的广泛能力。与先前的结论相反,胎儿-母体对血管紧张素II的升压敏感性没有差异,而胎盘血管系统对血管紧张素II的敏感性高于子宫胎盘循环。
Fetal sheep appear less responsive to infused angiotensin II (ANG II) than pregnant ewes. This may reflect a greater fetal metabolic clearance rate (MCRANGII) and thus lower plasma ANG II levels. We therefore determined fetal MCRANGII, half-life (T1/2), and placental removal of ANG II. Fetal sheep (n = 13; 113-139 days of gestation) received 0.573-5.73 micrograms ANG II/min iv for 30 min while arterial pressure and heart rate were monitored. Serial blood samples were obtained before and during a 30-min infusion to measure ANG II and calculate MCRANGII and after stopping the infusion to determine T1/2. MCRANGII was similar across gestation and at doses < or = 2.29 micrograms/min (683 +/- 49 vs. 74 +/- 5 ml.min-1.kg-1 for adults) but was 30-40% lower with 5.73 micrograms ANG II/min (494 +/- 57 ml.min-1.kg-1, P < 0.05). T1/2 was 15-21 s. Fetal placental ANG II removal averaged 87 +/- 3 vs. 20 +/- 6% for uteroplacental removal; this was unaffected by dose and was linear with plasma ANG II levels, and saturation was not evident. Plasma ANG II levels rose proportionally with infusion rate and did not change significantly over time; thus fetal plasma ANG II concentrations can be predicted from MCRANGII. Measured and predicted ANG II levels at each infusion rate and time point were similar: r = 0.87, slope = 0.87 (P < 0.001). At equivalent predicted plasma ANG II levels fetal and maternal pressor responses were similar (P > 0.1); however, increases in umbilical vascular resistance exceeded those in uteroplacental vascular resistance (P < 0.03). Fetal MCRANGII is approximately 10-fold greater than maternal, partially reflecting the extensive capacity of ANG II removal by the placental circulation. Contrary to previous conclusions, fetal-maternal pressor sensitivity to ANG II does not differ, whereas the placental vasculature is more sensitive to ANG II than the uteroplacental circulation.