Autacoids and Control of Human Placental Blood Flow

Abstract

SUMMARY1. 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.2. The low placental vascular resistance is due to a lack of nervous influences together with pregnancy-induced changes promoting vasodilatation. Increases occur in output of the vasodilators prostacyclin and nitric oxide and also in membrane sodium pump activity.3. Many autacoids are present in umbilical blood. Fetal vessels of the placenta develop intense vasoconstriction in the presence of some autacoids, such as thromboxane A2 and prostaglandins Fza and E2, and respond weakly to others, such as angiotensin I1 and 5-hydroxytryptamine. Nevertheless, vasodilator influences predominate.4. The diseases of pre-eclampsia and fetal growth retardation are associated with reduced output of nitric oxide and prostacyclin and with increased production of thromboxane A2 and endothelin-1 . These changes promote vasoconstriction, increased vascular sensitivity to vasoconstrictor stimuli, platelet aggregation and intravascular coagulation, retarding blood flow and fetoplacental growth.5. Aspirin and glyceryl trinitrate have been investigated for possible therapeutic use in preeclampsia and fetal growth retardation. Improved drug therapy is likely as knowledge increases of the importance of autacoids in normal placental function and in the changes that occur during disease.

Expression of Nitric Oxide Synthase Isoforms in the Human Placenta Is Not Altered by Labor

“…Besides vasodilative nitric oxide, various kinds of vasoconstrictive substances were hypothesized to be involved in the regulation of placental blood flow, such as endothelin-1, prostaglandin, and angiotensin-II [44,45]. Both endothelin-1 and angiotensin-II contract vascular smooth muscle, while nitric oxide and prostacyclin relax vascular smooth muscle and attenuate the contractive action of endothelin-1 and angiotensin-II [44,45]. However, the entire scheme of changes of expression during labor has yet to be fully elucidated.…”

Cloprostenol, a prostaglandin F2α analog, induces hypoxia in rat placenta: BOLD contrast MRI

“…Increasing evidence indicates that most embryonic losses that occur during early human pregnancy may be due to placental vasospasm generated by an impaired balance between vasodilatory and vasoconstrictory agents (1,2). Indeed, reduced placental vascular development and increased vascular resistance have been associated with early embryonic mortality (3,4).…”

Intrauterine Growth Retardation Is Associated With Reduced Activity and Expression of the Cationic Amino Acid Transport Systems y + /hCAT-1 and y + /hCAT-2B and Lower Activity of Nitric Oxide Synthase in Human Umbilical Vein Endothelial Cells

“…The release of local vasoactive molecules, such as nitric oxide (NO), from endothelium maintains appropriate placental blood flow, fetal nutrition, and oxygenation leading to normal fetal development and growth. 4 Endothelial NO synthesis results from conversion of L-arginine into L-citrulline by the Ca 2ϩ /calmodulin-dependent NO synthase (eNOS), a process associated with L-arginine transport via system y ϩ /CATs (Cationic Amino acid Transporters) in human umbilical vein endothelial cells (HUVECs). [5][6][7][8] L-Arginine transport is preferentially mediated by system y ϩ /CAT-1, a Na ϩ -independent, high-affinity transport system (K m Ϸ100 mol/L), sensitive to changes in membrane potential in HUVECs.…”