Ian M. Leitch

AUTACOIDS AND CONTROL OF HUMAN PLACENTAL BLOOD FLOW

1. Humans have a haemochorial, villous placenta. Uterine blood passes through maternal sinuses, bathing placental villi through which fetal blood circulates. Blood flow through each circulation is high and vascular resistance low. This haemodynamic situation is essential for efficient placental function.

Effect of inhibition of nitric oxide synthase and guanylate cyclase on hydralazine-induced vasodilatation of the human fetal placental circulation.

1. The vasodilator effects of hydralazine in vitro, using the Krebs’ perfused human placental lobule was studied. Single placental lobules were bilaterally perfused (maternal and fetal sides 5 mL/min each, 95% O2, 5% CO2, 37°C) and changes in fetal arterial pressure (FAP) and venous outflow (VO) were recorded.

Effects of Bufo marinus skin toxins on human fetal extracorporeal blood vesseLS

The effects of extracts of Bufo marinus toad skin toxin on human isolated umbilical arterial rings and the fetal vessels of perfused placentae were examined and compared with those of ouabain, an inhibitor of Na+/K(+)-ATPase. Umbilical artery rings and fetal vessels of the perfused placenta responded to extracts, or ouabain, with constriction which persisted after the removal of each agent. Extraction of the skin, using various solvents, revealed that the umbilical artery constriction was due mainly to the effects of water-soluble, polar compounds. Fractionation of a water extract and bioassay on the rat isolated aorta revealed maximum vasoconstrictor activity in a low mol. wt fraction. During Na+/K(+)-ATPase inactivation in the fetal circulation of the human placenta, by perfusion with K(+)-free Krebs solution, reactivation of the enzyme by K+ infusion caused vasodilatation. This effect was inhibited both by water extracts of load skin and by ouabain. Thus, properties of some of the endogenous compounds in B. marinus skin resemble those of ouabain, by causing persistent constriction of human fetal blood vessels. A component of the vasoconstrictor response probably results from inhibition of vascular smooth muscle Na+/K(+)-ATPase, but it is likely that a contribution is also made by additional vasoconstrictor substances contained in B. marinus toxin.

The control of fetal vascular resistance in the human placenta

Summary The human placenta, perfused after delivery at term, has revealed useful information about the control of placental fetal vascular resistance. The placenta is not innervated, resistance in the fetal circulation being controlled by myogenic mechanisms interacting with effects of autacoids. The fetal vasculature in vitro responds readily to some vasoconstrictor autacoids, particularly thromboxane A 2 and endothelin-1. However the vasoconstrictor concentrations needed are well in excess of those normally present in umbilical blood. Efficient mechanisms exist in the fetal circulation to maintain its normal low resistance to blood flow. Amongst these is the fetal endothelium (and possibly the trophoblast), which in response to endogenous peptides such as corticotropin-releasing hormone, and shear forces caused by passage of blood releases the dilator autacoid nitric oxide. This interacts with prostacyclin to cause cell membrane stabilization and activation of intracellular vasodilator mechanisms in vascular smooth muscle. Hypoxia in the perfused healthy placenta causes fetal vascular sensitivity changes to autacoids similar to those found in placentae from some pre-eclamptic women. In particular fetal placental release of NO appears to be impaired by hypoxia. We also conclude that hypoxia in the fetal circulation which may occur during preeclampsia (with or without restricted fetal growth) and in pregnancies uncomplicated with pre-eclampsia when fetal growth restriction is present, could possibly contribute to placental fetal vasoconstriction and reduced blood flow.

The control of fetal vascular resistance in the human placenta: A review

Summary The human placenta, perfused after delivery at term, has revealed useful information about the control of placental fetal vascular resistance. The placenta is not innervated, resistance in the fetal circulation being controlled by myogenic mechanisms interacting with effects of autacoids. The fetal vasculature in vitro responds readily to some vasoconstrictor autacoids, particularly thromboxane A2 and endothelin-1. However the vasoconstrictor concentrations needed are well in excess of those normally present in umbilical blood. Efficient mechanisms exist in the fetal circulation to maintain its normal low resistance to blood flow. Amongst these is the fetal endothelium (and possibly the trophoblast), which in response to endogenous peptides such as corticotropin-releasing hormone, and shear forces caused by passage of blood releases the dilator autacoid nitric oxide. This interacts with prostacyclin to cause cell membrane stabilization and activation of intracellular vasodilator mechanisms in vascular smooth muscle. Hypoxia in the perfused healthy placenta causes fetal vascular sensitivity changes to autacoids similar to those found in placentae from some pre-eclamptic women. In particular fetal placental release of NO appears to be impaired by hypoxia. We also conclude that hypoxia in the fetal circulation which may occur during preeclampsia (with or without restricted fetal growth) and in pregnancies uncomplicated with pre-eclampsia when fetal growth restriction is present, could possibly contribute to placental fetal vasoconstriction and reduced blood flow.