Role of endothelium-derived nitric oxide in maintenance of low fetal vascular resistance in placenta

Gude, Neil M; King, Roger G; Brennecke, Shaun P.

doi:10.1016/0140-6736(90)93374-x

Cited by 81 publications

(29 citation statements)

References 8 publications

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“…Therefore, we addressed the possibility that endogenous NO modulates HFPV in a similar manner as it alters reactivity to numerous pharmacological vasoconstrictors (19). In agreement with several previous studies (8,11,19,24), we found NO synthase inhibition by L-NAME to cause vasoconstriction during normoxia (confirming effectiveness of the dose). The hypoxic vasoconstriction, however, was unaltered (Fig.…”

Section: Discussionsupporting

confidence: 85%

Hypoxic fetoplacental vasoconstriction in humans is mediated by potassium channel inhibition

Hampl

Bíbová

Straňák

et al. 2002

American Journal of Physiology-Heart and Circulatory Physiology

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Fetal to maternal blood flow matching in the placenta, necessary for optimal fetal blood oxygenation, may occur via hypoxic fetoplacental vasoconstriction (HFPV). We hypothesized that HFPV is mediated by K+ channel inhibition in fetoplacental vascular smooth muscle, as occurs in several other O2-sensitive tissues. With the use of an isolated human placental cotyledon perfused at a constant flow rate, we found that hypoxia reversibly increased perfusion pressure by >20%. HFPV was unaffected by cyclooxygenase or nitric oxide synthase inhibition. HFPV and 4-aminopyridine, an inhibitor of voltage-dependent K+(Kv) channels, increased pressure in a nonadditive manner, suggesting they act via a common mechanism. Iberiotoxin, a large conductance Ca2+-sensitive K+(BKCa) channel inhibitor, had little effect on normoxic pressure. Immunoblotting and RT-PCR showed expression of several putative O2-sensitive K+ channels in peripheral fetoplacental vessels. In patch-clamp experiments with smooth muscle cells isolated from peripheral fetoplacental arteries, hypoxia reversibly inhibited Kv but not BKCa or ATP-dependent currents. We conclude that human fetoplacental vessels constrict in response to hypoxia. This response is largely mediated by hypoxic inhibition of Kv channels in the smooth muscle of small fetoplacental arteries.

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Section: Discussionsupporting

confidence: 85%

Hypoxic fetoplacental vasoconstriction in humans is mediated by potassium channel inhibition

Hampl

Bíbová

Straňák

et al. 2002

American Journal of Physiology-Heart and Circulatory Physiology

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“…L-NMMA competes with L-Arg, as well as L-lysine and L-ornithine, for the cationic amino acid system y+ transporter, whereas inhibitors such as NOARG and L-NAME, compete with L-leucine and L-isoleucine for the neutral amino acid transporter, system L. Co-incubation of placental sections with amino acids selective for either the system y+ or system L transporter had no apparent effect on [3H]-L-NOARG binding, suggesting that the radiolabelled inhibitor was not competing for an amino acid transport system but for the L-Arg recognition site of eNOS. Studies on isolated perfused placental cotyledons, in which NOS inhibitors were added to the foetoplacental circulation, have indicated that NO has a role in maintaining placental blood flow (Gude et al, 1990;Myatt et al, 1991;. However, the addition of NO to the intervillous space, rather than the foetoplacental circulation itself, has been found to have no effect on perfusion pressure (Eis et al, 1995), suggesting that trophoblast-derived NO may not have a significant influence on the tone of foetoplacental blood vessels.…”

Section: Tissuesmentioning

confidence: 99%

“…The release of NO has been demonstrated from human umbilical vein endothelium and exogenous NO shown to relax umbilical and chorionic plate artery preparations in vitro (Chaudhuri et al, 1991;Hull et al, 1994). NO attenuates the actions of vasoconstrictors in the foetoplacental circulation and inhibition either of NO synthesis, or of its action on vascular smooth muscle, increases basal perfusion pressure in the isolated human placental cotyledon (Gude et al, 1990;Myatt et al, 1991;. NO has also been implicated in the pathophysiology of pregnancy, there being evidence of endothelial dysfunction and imparied maternal NO production in pregnancies complicated by pre-eclampsia (PE) (Roberts & 1 Author for correspondence.…”

Section: Introductionmentioning

confidence: 99%

Nitric oxide synthase in human placenta and umbilical cord from normal, intrauterine growth‐retarded and pre‐eclamptic pregnancies

Rutherford¹,

McCarthy²,

Sullivan³

et al. 1995

British J Pharmacology

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“…Continuous local output of NO from placental vascular endothelial cells caused by flow-induced shear stress is an important mechanism contributing to the low resistance provided by the fetal vasculature to blood flow (Gude et al 1990;Myatt 1992). Nitric oxide can also be liberated by other stimuli, such as adenosine and other autacoids released within the fetal circulation.…”

Section: Vasodilator Influences In the Umbilical Circulationmentioning

confidence: 99%

Autacoids and Control of Human Placental Blood Flow

Boura

Walters

Read

et al. 1994

Clin Exp Pharma Physio

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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.

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Role of endothelium-derived nitric oxide in maintenance of low fetal vascular resistance in placenta

Cited by 81 publications

References 8 publications

Hypoxic fetoplacental vasoconstriction in humans is mediated by potassium channel inhibition

Hypoxic fetoplacental vasoconstriction in humans is mediated by potassium channel inhibition

Nitric oxide synthase in human placenta and umbilical cord from normal, intrauterine growth‐retarded and pre‐eclamptic pregnancies

Autacoids and Control of Human Placental Blood Flow

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