The Experts below are selected from a list of 291 Experts worldwide ranked by ideXlab platform
Ingrid Fleming - One of the best experts on this subject based on the ideXlab platform.
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Myoendothelial Gap Junctions The Gap Is There, but Does EDHF Go Through It?
2016Co-Authors: Ingrid FlemingAbstract:The endothelium-derived Autacoids, nitric oxide (NO)and prostacyclin (PGI2), play a crucial role in theregulation of local vascular tone. However, these two factors alone cannot account for all of the endothelium-dependent dilator responses observed in a number of arteries, most notably in coronary, mesenteric, carotid, and renal arteries. Because endothelium-dependent, but NO synthase and cyclo-oxygenase inhibitor-insensitive dilator responses are associated with vascular smooth muscle hyperpolariza-tion, the existence of a third dilator Autacoid, an endotheli-um-derived hyperpolarizing factor (EDHF), has been proposed. By monitoring the membrane potential of detector vascular smooth muscle cells situated downstream from donor endo-thelial cells, it is possible to monitor the production of an EDHF.1 On the other hand, there has been no convincing demonstration of the transfer of an NO/PGI2-independen
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Vascular Endothelium and Blood Flow
Handbook of experimental pharmacology, 2006Co-Authors: Rudi Busse, Ingrid FlemingAbstract:Major advances have been made over the last decade towards the elucidation of the molecular mechanisms involved in the endothelium-dependent regulation of vascular tone and blood flow. While the primary endothelium-derived vasodilator Autacoid is nitric oxide, it is clear that epoxyeicosatrienoic acids and other endothelium-derived hyperpolarising factors, as well as endothelin-1 and reactive oxygen species, play a significant role in the regulation of vascular tone and gene expression. This review is intended as an overview of the signalling mechanisms that link haemodynamic stimuli (such as shear stress and cyclic stretch) and endothelial cell perturbation to the activation of enzymes generating vasoactive Autacoids.
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Regulation of endothelium-derived vasoactive Autacoid production by hemodynamic forces.
Trends in pharmacological sciences, 2003Co-Authors: Rudi Busse, Ingrid FlemingAbstract:Endothelial cells, which are situated at the interface between blood and the vessel wall, have a crucial role in controlling vascular tone and homeostasis, particularly in determining the expression of pro-atherosclerotic and anti-atherosclerotic genes. Many of these effects are mediated by changes in the generation and release of endothelium-derived Autacoids [from the Greek autos (self) and akos (remedy)], which are generally short-lived and locally acting. In vivo, endothelial cells are constantly subjected to mechanical stimulation, which in turn determines the acute production of Autacoids and the levels of Autacoid-producing enzymes.
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Cytochrome P450 2C is an EDHF synthase in coronary arteries.
Trends in cardiovascular medicine, 2000Co-Authors: Ingrid FlemingAbstract:Studies designed to elucidate the identity of the potent vasodilator Autacoid endothelium-derived hyperpolarizing factor (EDHF) in the coronary vascular bed have highlighted a role for vascular cytochrome P450 (CYP) enzymes in cardiovascular homeostasis. Not only is there strong evidence suggesting that the putative coronary EDHF synthase is an endothelially expressed CYP epoxygenase, but CYP products such as epoxyeicosatrienoic acids and reactive oxygen species have been implicated in the regulation of intracellular signalling cascades and vascular cell proliferation.
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NO: the primary EDRF.
Journal of molecular and cellular cardiology, 1999Co-Authors: Ingrid Fleming, Rudi BusseAbstract:Abstract Since the discovery of an endothelium-derived relaxing factor (EDRF) by Furchgott and Zawadzki (Furchgott and Zawadzki, 1980), which was later identified as nitric oxide (NO) (Ignarroet al., 1987; Palmeret al., 1987; Furchgott, 1988), it has become clear that there are a number of additional endothelium-derived vasodilator and vasoconstrictor Autacoids (endothelin-1, prostaglandin H2and the endothelium-derived hyperpolarizing factor: EDHF). None of these Autacoids play such a central role in the regulation of vascular tone and homeostasis as the primary EDRF, the free radical NO, which is generated via a five-electron oxidation of a guanidino nitrogen from L-arginine by an NO synthase (NOS).
Rudi Busse - One of the best experts on this subject based on the ideXlab platform.
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Vascular Endothelium and Blood Flow
Handbook of experimental pharmacology, 2006Co-Authors: Rudi Busse, Ingrid FlemingAbstract:Major advances have been made over the last decade towards the elucidation of the molecular mechanisms involved in the endothelium-dependent regulation of vascular tone and blood flow. While the primary endothelium-derived vasodilator Autacoid is nitric oxide, it is clear that epoxyeicosatrienoic acids and other endothelium-derived hyperpolarising factors, as well as endothelin-1 and reactive oxygen species, play a significant role in the regulation of vascular tone and gene expression. This review is intended as an overview of the signalling mechanisms that link haemodynamic stimuli (such as shear stress and cyclic stretch) and endothelial cell perturbation to the activation of enzymes generating vasoactive Autacoids.
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Regulation of endothelium-derived vasoactive Autacoid production by hemodynamic forces.
Trends in pharmacological sciences, 2003Co-Authors: Rudi Busse, Ingrid FlemingAbstract:Endothelial cells, which are situated at the interface between blood and the vessel wall, have a crucial role in controlling vascular tone and homeostasis, particularly in determining the expression of pro-atherosclerotic and anti-atherosclerotic genes. Many of these effects are mediated by changes in the generation and release of endothelium-derived Autacoids [from the Greek autos (self) and akos (remedy)], which are generally short-lived and locally acting. In vivo, endothelial cells are constantly subjected to mechanical stimulation, which in turn determines the acute production of Autacoids and the levels of Autacoid-producing enzymes.
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NO: the primary EDRF.
Journal of molecular and cellular cardiology, 1999Co-Authors: Ingrid Fleming, Rudi BusseAbstract:Abstract Since the discovery of an endothelium-derived relaxing factor (EDRF) by Furchgott and Zawadzki (Furchgott and Zawadzki, 1980), which was later identified as nitric oxide (NO) (Ignarroet al., 1987; Palmeret al., 1987; Furchgott, 1988), it has become clear that there are a number of additional endothelium-derived vasodilator and vasoconstrictor Autacoids (endothelin-1, prostaglandin H2and the endothelium-derived hyperpolarizing factor: EDHF). None of these Autacoids play such a central role in the regulation of vascular tone and homeostasis as the primary EDRF, the free radical NO, which is generated via a five-electron oxidation of a guanidino nitrogen from L-arginine by an NO synthase (NOS).
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pulsatile stretch and shear stress physical stimuli determining the production of endothelium derived relaxing factors
Journal of Vascular Research, 1998Co-Authors: Rudi Busse, Ingrid FlemingAbstract:Mechanical forces generated at the endothelium by fluid shear stress and pulsatile stretch are important in ensuring the continuous release of vasoactive endothelial Autacoids. Although the mechanism
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Endothelium-Derived Hyperpolarizing Factor, But Not Nitric Oxide, Is Reversibly Inhibited by Brefeldin A
Hypertension, 1997Co-Authors: Johann Bauersachs, Rudiger Popp, Ingrid Fleming, Dimitri Scholz, Rudi BusseAbstract:Abstract The subcellular localization of the enzymes synthesizing endothelium-derived vasodilator Autacoids has been proposed to play a role in determining the ability of endothelial cells to enhance Autacoid production in response to stimulation. We therefore investigated the effects of brefeldin A–induced disruption of the Golgi apparatus and Golgi-plasma membrane trafficking on the production of nitric oxide (NO), prostacyclin, and the endothelium-derived hyperpolarizing factor (EDHF) by native and cultured endothelial cells. In porcine coronary artery segments, brefeldin A (35 μmol/L, 90 minutes) did not affect relaxations to sodium nitroprusside or the K + channel opener cromakalim but elicited a rightward shift in the concentration-response curve to bradykinin without altering the maximum vasodilator response (R max ). Brefeldin A failed to attenuate the bradykinin-induced, NO-mediated relaxation under depolarizing conditions but inhibited the bradykinin response under conditions of combined cyclooxygenase/NO synthase blockade, suggesting that this agent selectively interferes with the production of EDHF. Indeed, incubation of porcine coronary arteries with brefeldin A, which did not affect the bradykinin-induced accumulation of either cyclic GMP or 6-keto-prostaglandin F 1α , markedly and reversibly attenuated the EDHF-mediated hyperpolarization of detector smooth muscle cells in a patch-clamp bioassay system. The microtubule destabilizer nocodazole also affected both the EC 50 and R max to bradykinin in porcine coronary arteries. Since EDHF is thought to be a cytochrome P450–derived metabolite of arachidonic acid and both brefeldin A and nocodazole are known to interfere with the targeting of cytochrome P450 from the Golgi apparatus to the plasma membrane, it is conceivable that brefeldin A inhibits EDHF formation by preventing the targeting of the EDHF-synthesizing enzymes to the plasma membrane.
A.l.a. Boura - One of the best experts on this subject based on the ideXlab platform.
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The control of fetal vascular resistance in the human placenta: A review
Placenta, 1998Co-Authors: A.l.a. Boura, Ian M. Leitch, M.a. Read, W.a.w. WaltersAbstract: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.
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The control of fetal vascular resistance in the human placenta
Placenta, 1996Co-Authors: A.l.a. Boura, Ian M. Leitch, M.a. Read, W.a.w. WaltersAbstract: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.
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Autacoids and control of human placental blood flow.
Clinical and experimental pharmacology & physiology, 1994Co-Authors: A.l.a. Boura, M.a. Read, William A.w. Walters, Ian M. LeitchAbstract:SUMMARY 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. 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 F2α and E2, and respond weakly to others, such as angiotensin II 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 feto-placental growth. 5. Aspirin and glyceryl trinitrate have been investigated for possible therapeutic use in pre-eclampsia 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.
Ian M. Leitch - One of the best experts on this subject based on the ideXlab platform.
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The control of fetal vascular resistance in the human placenta: A review
Placenta, 1998Co-Authors: A.l.a. Boura, Ian M. Leitch, M.a. Read, W.a.w. WaltersAbstract: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.
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The control of fetal vascular resistance in the human placenta
Placenta, 1996Co-Authors: A.l.a. Boura, Ian M. Leitch, M.a. Read, W.a.w. WaltersAbstract: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.
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Autacoids and control of human placental blood flow.
Clinical and experimental pharmacology & physiology, 1994Co-Authors: A.l.a. Boura, M.a. Read, William A.w. Walters, Ian M. LeitchAbstract:SUMMARY 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. 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 F2α and E2, and respond weakly to others, such as angiotensin II 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 feto-placental growth. 5. Aspirin and glyceryl trinitrate have been investigated for possible therapeutic use in pre-eclampsia 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.
W.a.w. Walters - One of the best experts on this subject based on the ideXlab platform.
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The control of fetal vascular resistance in the human placenta: A review
Placenta, 1998Co-Authors: A.l.a. Boura, Ian M. Leitch, M.a. Read, W.a.w. WaltersAbstract: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.
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The control of fetal vascular resistance in the human placenta
Placenta, 1996Co-Authors: A.l.a. Boura, Ian M. Leitch, M.a. Read, W.a.w. WaltersAbstract: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.
