Moritz K M, Campbell D J, Wintour E M
Howard Florey Institute of Experimental Physiology and Medicine, University of Melbourne, Parkville 3010, Australia.
Am J Physiol Regul Integr Comp Physiol. 2001 Feb;280(2):R404-9. doi: 10.1152/ajpregu.2001.280.2.R404.
In the adult animal, ANG-(1-7) may counterbalance some effects of ANG II. Its effects in the fetus are unknown. Basal ANG-(1-7), ANG I, ANG II, and renin concentrations were measured in plasma from ovine fetuses and their mothers (n = 10) at 111 days of gestation. In the fetus, concentrations of ANG I, ANG-(1-7), and ANG II were 86 +/- 21, 13 +/- 2, and 14 +/- 2 fmol/ml, respectively. In the ewe, concentrations of ANG I were significantly lower (20 +/- 4 fmol/ml, P < 0.05) as were concentrations of ANG-(1-7) (2.9 +/- 0.6 fmol/ml), whereas ANG II concentrations were not different (10 +/- 1 fmol/ml). Plasma renin concentrations were higher in the fetus (4.8 +/- 1.1 pmol ANG I x ml(-1) x h(-1)) than in the ewe (0.9 +/- 0.2 pmol x ml(-1) x h(-1), P < 0.05). Infusion of ANG-(1-7) (approximately 9 microg/h) for a 3-day period caused a significant increase in plasma concentrations of ANG-(1-7) reaching a maximum of 448 +/- 146 fmol/ml on day 3 of infusion. Plasma levels of ANG I and II as well as renin were unchanged by the infusion. Urine flow rate, glomerular filtration rate, and fetal arterial blood pressure did not change and were not different than values in fetuses receiving a saline infusion for 3 days (n = 5). However, the osmolality of amniotic and allantoic fluid was significantly higher in fetuses that received ANG-(1-7). Also, compared with the saline-infused animals, mRNA expression levels of renin, the AT(1) receptor, and AT(2) receptor were elevated in kidneys of fetuses that received infusions of ANG-(1-7). Infusion of an ANG-(1-7) antagonist ([D-Ala(7)]-ANG-(1-7), 20 microg/h) for 3 days had no effect on fetal blood pressure or renal function. In conclusion, although infusion of ANG-(1-7) did not affect fetal urine flow rate, glomerular filtration rate, or blood pressure, changes in fetal fluids and gene expression indicate that ANG-(1-7) may play a role in the fetal kidney.
在成年动物中,血管紧张素-(1-7)(ANG-(1-7))可能会抵消血管紧张素II(ANG II)的某些作用。其对胎儿的作用尚不清楚。在妊娠111天时,测量了绵羊胎儿及其母亲(n = 10)血浆中的基础ANG-(1-7)、血管紧张素I(ANG I)、ANG II和肾素浓度。在胎儿中,ANG I、ANG-(1-7)和ANG II的浓度分别为86±21、13±2和14±2 fmol/ml。在母羊中,ANG I的浓度显著较低(20±4 fmol/ml,P < 0.05),ANG-(1-7)的浓度也较低(2.9±0.6 fmol/ml),而ANG II的浓度没有差异(10±1 fmol/ml)。胎儿的血浆肾素浓度高于母羊(4.8±1.1 pmol ANG I×ml⁻¹×h⁻¹)(0.9±0.2 pmol×ml⁻¹×h⁻¹,P < 0.05)。连续3天输注ANG-(1-7)(约9μg/h)导致血浆ANG-(1-7)浓度显著升高,在输注第3天达到最高值448±146 fmol/ml。输注后ANG I和ANG II的血浆水平以及肾素水平未发生变化。尿流率、肾小球滤过率和胎儿动脉血压没有改变,与接受3天生理盐水输注的胎儿(n = 5)的值没有差异。然而,接受ANG-(1-7)输注的胎儿羊膜液和尿囊液的渗透压显著更高。此外,与生理盐水输注组动物相比,接受ANG-(1-7)输注的胎儿肾脏中肾素、AT(1)受体和AT(2)受体的mRNA表达水平升高。连续3天输注ANG-(1-7)拮抗剂([D-Ala(7)]-ANG-(1-