Delayed vasoconstriction of the umbilico-placental circulation by angiotensin in fetal sheep.
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Angiotensin II↗
Biomedical subjects
J J Faber
Publications and source records attributed to J J Faber.
Angiotensin mediated interaction of fetal kidney and placenta in the control of fetal arterial pressure and its role in hydrops fetalis.
Fetal cardiovascular control is effected by an interaction of the fetal somatic and placental circulations. Three primary regulatory mechanisms are involved: transplacental transfer of extracellular fluid, driven by a difference in hydrostatic and oncotic pressures; modulation of fetal placental and somatic vascular resistances by means of blood pressure controlled production of angiotensin; and somatic autoregulation of flow. A systems analysis incorporates these and other fetal cardiovascular functions and this analysis was modelled for computer simulation. Given physiologically plausible values for known cardiovascular parameters in the fetal sheep, the model reproduced in detail a variety of experimental protocols with known outcomes; these included the normal fetus, the fetus after bilateral nephrectomy, the nephrectomized fetus infused with angiotensin, the intact fetus infused with NaCl solutions, the fetus with lymphatic obstruction and the severely anaemic fetus. The systems analysis demonstrated that fetal cardiac failure constituted the strongest stimulus for the formation of fetal oedema of any tested pathological intervention.
Angiotensin II↗
The non-steady state of pregnancy.
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Animals↗
Graphic format for teaching long-term control of systemic arterial pressure.
Circulatory homeostasis is a difficult notion. The graphic format presented here facilitates the teaching of long-term control of systemic arterial blood pressure and cardiac output. It is based on the view that the following four "function curves" cooperate in long-term regulation: the relation between blood volume and ventricular filling pressure, the relation between ventricular filling pressure and cardiac output, the relation between cardiac output and peripheral resistance, and the relation between arterial pressure and natriuresis. Positioning the function curves in the format presented here clarifies their cooperativity. The distinction between a nonsteady state and a steady state deserves emphasis. Long-term pathophysiology of the circulation is most easily taught on the basis of the assumption that, generally, there will be a steady state. The format clarifies why some known physiological relations are almost impossible to demonstrate in the intact organism, and it discourages explanations of pathophysiology that are not firmly based on physiology.
Audiovisual Aids↗
Concentrations of Na+ and Cl- in transplacental ultrafiltrate in sheep.
1. Maternal blood was made transiently hypertonic by rapid I.V. infusion of a concentrated mannitol solution into pregnant ewes bearing lambs with an indwelling flow sensor and vascular catheters. 2. The transplacental flows of water and of Na+ and Cl- were calculated from the umbilical arteriovenous differences in the concentrations of 125I-labelled albumin and electrolytes, and the fetal placental blood flow. 3. The reflection coefficients of Na+ and Cl- were calculated by means of the Patlak equation and found to be 0.85 +/- 0.04 and 0.68 +/- 0.04 (means +/- S.E.M.). The filtration coefficient was 1.02 x 10(-7) +/- 0.12 x 10(-7) cm5 dyne-1 s-1. 4. The results fitted best to an equivalent pore radius in the placental barrier smaller than the currently accepted 0.44 nm but not less than 0.35 nm.
Animals↗
Transplacental clearances of inert hydrophilic tracers in rabbits of 18 days gestation.
Transplacental clearances were measured for radiolabelled Cl-, SO4(2-), mannitol, sucrose, raffinose, PEG-900 and inulin. Maternal placental blood flows were measured with radiolabelled microspheres. At 18 days of gestation (term 31 days), the fetuses and extra-fetal fluids were growing at 55 and 32 per cent per day, accounting for a net transplacental filtration rate of 14.2 nl/sec per gram placental weight. Pore theory and a least squares fit of the Patlak equation yielded an equivalent pore radius of 1.75 nm. It was demonstrated that the clearance of the largest tracer, inulin, was 30 times higher than it would have been in the absence of net filtration. Comparison with literature data showed that there was a small increase in placental permeability per gram placenta between 14 and 18 days of gestation but that the increase between 18 and 28 days of gestation was about 14-fold for Cl- and 300-fold for inulin. There was no evidence for a decreasing equivalent pore radius in the course of gestation from 14-18 days.
Animals↗
Excess extrafetal fluid without demonstrable changes in placental concentration gradients after week-long infusions of angiotensin into fetal lambs.
It is known that a week-long infusion of angiotensin into fetal sheep produces polyhydramnios. The purpose of the present experiments was to determine whether an increased osmotic force across the placental barrier could account for the excess transfer of water. Six fetuses with indwelling catheters were infused with angiotensin-I and one with angiotensin-II; all, except one fetus in the first group, developed gross polyhydramnios. None of the transplacental concentration differences of the small plasma solutes Na+, Cl-, HCO3-, K+, urea, or glucose showed a demonstrable change and the same was true of the transplacental difference in freezing point osmolality and for the transplacental difference in plasma protein concentration. It is concluded that the infusion of angiotensin at a low dose rate is a reliable protocol for producing polyhydramnios. However, the present findings lend no support to the hypothesis that a primary change in transplacental osmotic force is the cause of the increased transplacental water transfer in this form of polyhydramnios. Alternative hypotheses are discussed in the light of recent discoveries.
Angiotensin I↗
Interrelationships between the renin angiotensin system and uteroplacental blood flow--a recent perspective.
In pregnancy, the maternal circulating renin-angiotensin system (RAS) and uteroplacental tissue RAS has been thought to support maternal placental flow by raising maternal arterial pressure or changing placental vascular resistance. Also, the placenta or uterus may alter maternal circulating RAS. Recent studies in the authors' laboratory using chronically catheterized rabbits are compared with previous studies on interactions between the RAS and uteroplacental flow. When uterine driving pressure was reduced either mechanically or after converting enzyme inhibition, maternal placental flow decreased in proportion to change in driving pressure; myoendometrial flow did not change. Angiotensin II (AII) infusion to increase pressure by 21 +/- 2 mm Hg decreased placental but not myoendometrial flow. Thus, there is no evidence that maternal placental flow is autoregulated or supported by a specific renin-angiotensin mechanism. Normally, there is no net uterine release or uptake of active plasma renin activity, AI, or AII, but there is a small net release of trypsin-activated plasma renin activity (tPRA), presumably prorenin. Distal aortic occluder inflation produced upper-body hypertension, and uterine release of tPRA increased. There was a significant uterine arteriovenous concentration difference for AII during AII infusion. These methods are adaptable for studying interactions between uteroplacental flow and other vasoactive agents.
Angiotensin II↗
Substantial reductions in blood pressure after bilateral nephrectomy in fetal sheep.
The role of the kidneys in the maintenance of arterial blood pressure was examined in fetal sheep. Surgery was performed on 11 pregnant sheep (8 twin pregnancies) at approximately 125 days. All 19 fetuses were instrumented with hindlimb arterial and venous catheters. Eleven of the fetuses (but only 1 of each twin) were also bilaterally nephrectomized. Fetal arterial blood pressure was measured several times between 2 and 14 days after surgery. Arterial blood pressure in the intact fetuses increased from 44 +/- 1 to 47 +/- 1 mmHg (SE) but gradually decreased from 37 +/- 4 to 25 +/- 3 mmHg in the nephrectomized group. Whereas the arterial blood pressures measured on the first day of the experiment were not statistically significantly different between the two groups, by the final day of the experiment the arterial blood pressure of the intact fetuses was much higher than that of the nephrectomized fetuses. Venous blood pressure was similar in the two groups. We conclude that bilateral nephrectomy in fetal sheep not only stops the normal gestational increase in arterial blood pressure but also leads to a progressive decline.
Animals↗
Hydrops fetalis in nephrectomized fetal lambs infused with angiotensin I.
Nine bilaterally nephrectomized fetal sheep were infused for 6 days with angiotensin I in sterile water, and five nephrectomized fetal sheep were infused for 6 days with water alone. Total dose of angiotensin was 13.8 +/- 8.6 (SD) mg/kg fetal dry wt, and the total volumes of infused water were 303 +/- 201 and 423 +/- 164 ml, respectively. Of the fetuses infused with angiotensin I, one was of normal appearance, two showed moderate hydrops fetalis, and the remaining fetuses were grossly hydropic. All water-infused fetuses were normal. Their wet-to-dry weight ratios were 7.98 and 6.36 (P < 0.015), representing a 25% of normal body weight excess of water in the angiotensin I-infused fetuses. Six days of angiotensin I infusion caused a gradual rise in fetal arterial blood pressure from 37 +/- 15 to 81 +/- 15 mmHg (P < 0.05) and a gradual rise in venous blood pressure from 2.7 +/- 1.0 to 10.5 +/- 1.7 mmHg (P < 0.05). It was concluded that the fetal edema was due to the elevation in venous pressure. Plasma concentrations of Na+, K+, Cl-, HCO3-, total alpha-amino acids, fructose, glucose, and lactate in the fetus and the ewe did not identify an osmotically active solute responsible for the transplacental attraction of excess water into the conceptus, and the mechanism that attracted this excess water across the placenta remains unclear.
Angiotensin I↗
Maternal placental blood flow is reduced in proportion to reduction in uterine driving pressure.
The relationship between uterine driving pressure and maternal placental blood flow was studied after inflation of an aortic occluder previously placed between the renal and ovarian arteries in 10 conscious pregnant rabbits at 28 +/- 1 (mean +/- SEM) d of a 30- to 31-d gestation to test the hypothesis that there is autoregulation of maternal placental blood flow. After control measurements, the femoral artery pressure was reduced 22 +/- 3% from 83 +/- 5 mm Hg and clamped at 65 +/- 4 mm Hg (p < 0.001) for 54 +/- 4 min by servo control. Carotid artery pressure increased from 86 +/- 5 to 98 +/- 6 mm Hg (p < 0.01). There was no change in cardiac output (839 +/- 78 vs 814 +/- 64 mL/min; NS), upper-body flow (651 +/- 62 vs 671 +/- 55 mL/min; NS), or renal flow (111 +/- 14 vs 104 +/- 8 mL/min; NS). Blood flow to tissues below the occluder decreased from 188 +/- 18 to 143 +/- 14 mL/min for the lower body (p < 0.05), 153 +/- 15 to 116 +/- 11 mL/min for the hindquarters (p < 0.05), and 17.7 +/- 1.9 to 12.9 +/- 1.4 mL/min for 13 pregnant uterine horns (p < 0.05). Placental flow to live fetuses per horn decreased from 13.0 +/- 1.9 to 8.9 +/- 1.2 mL/min (p < 0.01), whereas there was no significant change in myoendometrial flow (4.0 +/- 0.3 vs 3.5 +/- 0.5 mL/min; NS). Uterine oxygen consumption was unchanged (1.15 +/- 0.16 vs 1.06 +/- 0.13 mL/min; NS).(ABSTRACT TRUNCATED AT 250 WORDS)
Angiotensin I↗
Diffusion permeability of the immature placenta of the rabbit embryo to inert hydrophilic molecules.
The clearances of a series of hydrophilic probes (radii of 2-10 A) were determined in rabbit placentas of 13-15 days of gestation (term, 31 days). Maternal placental blood flows were measured by means of radiolabeled microspheres. None of the transfers of the tracers were limited by maternal or embryonic arteriovenous differences in the placenta, and the clearances decreased with increasing molecular radius. The transplacental water filtration rate calculated from conceptual growth was comparable in magnitude to the clearances of the largest tracers. Application of Patlak's modification of the Hertzian equation and pore theory suggested an equivalent pore radius of 17 A. Placental permeability surface area products computed from this value decreased much more steeply with increasing molecular dimension than the measured clearances, suggesting a highly significant contribution by filtration despite the very large diffusional gradients that existed under the experimental conditions. The results indicate that the size selectivity of the hemochorial embryo placenta in vivo is not very significant, and that under normal conditions filtrate of maternal plasma constitutes a major contributor to embryonic supply.
Animals↗
Convention for reporting amniotic fluid pressure.
A proposed convention sets zero pressure at atmospheric pressure at the level of the surface supporting the supine patient and takes the cm of water as the unit of measurement. This ensures that measurements made in different clinics will be comparable. Statements about 'higher' and 'lower' pressures, in different patients or in the same patient in different situations, should specify the level of the uterus to which the statement applies.
Amniotic Fluid↗
Effects of captopril on blood pressure, placental blood flow and uterine oxygen consumption in pregnant rabbits.
Uterine renin may regulate uteroplacental blood flow locally through changes in vascular resistance or systemically by supporting arterial blood pressure. Captopril (5 mg/kg) was given i.v. to 14 conscious pregnant rabbits at day 27.5 +/- 0.3 of gestation for the purpose of investigating the effects of angiotensin converting enzyme inhibition on uteroplacental blood flow and oxygen consumption. Control measurements (mean +/- S.E.M.) were compared to measurements made at 1 hr (n = 14) and at 3 to 4 hr (n = 7). Arterial blood pressure decreased from 80 +/- 3 to 66 +/- 3 mm Hg, P less than .01, and then declined further to 56 +/- 4 mm Hg, P less than .01. Cardiac output was unchanged at 1 hr, 799 +/- 79 vs. 705 +/- 61 ml/min, but was decreased to 634 +/- 29 ml/min by 3 to 4 hr, P less than .01. There was no change in renal blood flow from 102 +/- 13 ml/min. Total uterine blood flow decreased from 37 +/- 5 to 29 +/- 5 ml/min, P less than .01, and then to 23 +/- 1 ml/min, P less than .01, whereas placental blood flow decreased from 25 +/- 4 to 19 +/- 3 to 15 +/- 3 ml/min, P less than .01; there was no significant change in myoendometrial flow. Oxygen delivery per uterine horn decreased from 2.4 +/- 0.3 to 1.8 +/- 0.4 to 1.6 +/- 0.2 ml/min, P less than .005. Oxygen consumption per horn decreased from 1.31 +/- 0.14 to 1.05 +/- 0.15 ml/min by 1 hr, P less than .05, and there was no further decrease.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Filtration of water from mother to conceptus via paths independent of fetal placental circulation in sheep.
1. Four pregnant ewes were operated on at 121-126 days of gestation. An electromagnetic flow sensor and an inflatable occluder were placed on the maternal common internal iliac artery. The ovarian arteries and veins were ligated. Indwelling catheters were placed in a maternal femoral artery and uterine vein and in the amniotic and allantoic fluids. An inflatable occluder was placed around the umbilical cord, close to the fetal abdomen. 2. Eight to nine days after surgery, the cord was occluded, the fetus killed and uterine blood flow reduced to one-quarter of its control value. The rate of water loss from the uterine circulation was calculated from blood flow and the venoarterial difference in blood osmolality. The amniotic and allantoic fluids were made hypertonic by infusion of 2 l into each sac of a solution of 1.5 mol of mannitol per litre of saline. The rate of water loss from the maternal uterine circulation was then measured five times over the next 4.5 h. 3. The combined filtration coefficient surface area product of the interfaces between maternal blood and the amniotic and allantoic sacs, normalized per kilogram fetal body weight, was (2.8 +/- 0.5) x 10(-6) cm3 s-1 kPa-1 kg-1 (mean +/- S.E.M).
Allantois↗
Model study of placental water transfer and causes of fetal water disease in sheep.
The purpose of the computer simulation was to use experimentally measured parameters of placental water transfer to compute conceptual water acquisition during the last third of ovine pregnancy and to evaluate the possible role of each of these parameters in the pathophysiology of polyhydramnios. Total conceptual water at birth was almost insensitive to the value of the placental filtration coefficient. It was more sensitive to fetal and maternal placental blood flows, the concentrations of actively transported or metabolically produced solutes in fetal plasma (bicarbonate, fructose, alpha-amino acids, urea, lactate), and the hydrostatic pressure difference across the placental barrier. It was quite sensitive to the NaCl reflection coefficient and permeability. We conclude that the actively transported or produced solutes in fetal plasma constitute a primary driving force. The opposing diffusion gradient of NaCl, and to a much lesser extent that of glucose, are essential to restrain the process. The causes of polyhydramnios in this species are, in order of probability, an increase in the placental diffusion permeability of NaCl, a decrease in the placental reflection coefficient for NaCl, or an increase in the concentration of an osmotically effective solute in fetal plasma, by active transport or metabolic production.
Animals↗
Animal model for polyhydramnios.
Chronic intravenous infusion of angiotensin 1 [182 micrograms/(kg.day)] into fetal lambs caused gross polyhydramnios. Infusions of comparable volumes of vehicle or lower concentrations of angiotensin 1 [48 micrograms/(kg.day)] did not cause gross polyhydramnios.
Angiotensin I↗