Plasma-Endothelin bei Normalpersonen und Patienten mit nephrologisch-rheumatologischen und kardiovaskulären Erkrankungen

Schrader, J; Tebbe, Ulrich; Borries, M.; Ruschitzka, Frank; Schoel, G.; Kandt, M; Warneke, G.; Züchner, C; Mh, Weber; Neu, U.

doi:10.1007/bf01647248

Cited by 31 publications

(6 citation statements)

References 28 publications

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“…Conflicting results have been reported on endothelin plasma levels in pregnant women with hypertension. Some authors observed decreased plasma endothelin levels in women with hypertension and proteinuria (Schrader et al . 1990), and recent reports showed significantly higher plasma endothelin levels in women with pregnancy‐induced hypertension compared with normotensive pregnant women (Kamoi et al .…”

Section: Discussionmentioning

confidence: 99%

Evidence against a pathogenetic role for endothelin in pre‐eclampsia

Benigni

Orisio

Gaspari

et al. 1992

BJOG

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Objective To assess whether increased placental or systemic endothelin synthesis has a pathogenic role in pre‐eclampsia (gestational proteinuric hypertension). Design Prospective observations study. Subjects 19 women with pre‐eclampsia and 10 healthy pregnant women were studied. All were in the last trimester. Main outcome measures Preproendothelin‐1 gene expression by Northern blot analysis and generation of endothelin‐1 precursor, big‐endothelin‐1, and endothelin isoforms, namely endothelin‐1, 2 and 3, were assessed by specific radioimmunoassays, in placental tissue. Plasma endothelin‐1 levels and urinary excretion of big‐endothelin‐1 and endothelin‐1 were measured. Results Placental preproendothelin‐1 gene expression and immunoreactive bigendothelin‐1 and endothelin‐1, 2 and 3, were comparable in placental tissue from pre‐eclamptic and normal pregnant women. Plasma levels of endothelin‐1 did not differ between pre‐eclamptic and normal pregnancies. In contrast, urinary excretion of endothelin‐1, which is likely to reflect the renal synthesis of the peptide, was significantly decreased in pre‐eclamptic, as compared with normal pregnant women. This was not due to a decreased renal generation of endothelin‐1 precursor, since urinary excretion of big‐endothelin‐1 did not differ between pre‐eclamptic and normal pregnancies. These data suggest an increased renal endothelin‐1 breakdown in pre‐eclampsia. Conclusions Endothelin is unlikely to play a role in the pathogenesis of pre‐eclampsia. Instead, an increased renal breakdown may have a role in limiting the negative effects of other vasoactive factors on the renal circulation.

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Section: Discussionmentioning

confidence: 99%

Evidence against a pathogenetic role for endothelin in pre‐eclampsia

Benigni

Orisio

Gaspari

et al. 1992

BJOG

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“…In clinical practice, plasma ET levels are significantly elevated in the patients with cirrhosis. 9 These studies raise the possibility that ET-1 may be involved in the pathogenesis of portal hypertension in various liver diseases.…”

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confidence: 99%

Endothelin-1-induced vasoconstriction causes a significant increase in portal pressure of rat liver: Localized constrictive effect on the distal segment of preterminal portal venules as revealed by light and electron microscopy and serial reconstruction

et al. 1998

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Portal hypertension is a clinical syndrome caused by a pathological increase in portal pressure usually accompanied by complications such as ascites, esophageal varices, and hepatic encephalopathy. In cirrhosis, decreased sinusoidal caliber and impaired sinusoidal wall elasticity are considered to be responsible for the increased portal pressure. [1][2][3] In addition to structural changes, humoral factors with vasoactivity may modify the resistance of portal vasculature and contribute to the pathogenesis. Endothelin-1 (ET-1), a peptide produced by vascular endothelial cells, induces strong contraction of perivascular smooth muscles. 4 The liver is considered to be particularly sensitive to the constriction action of ET-1 because systemic infusion of low-dose ET-1, which exerts relatively little effect on systemic pressure, can cause an increase in portal pressure. 5 Elevation of portal pressure occurs more dramatically by the intraportal infusion of ET-1. 5,6 The sinusoids and presinusoidal portal venules were thought to be involved. 5 It is demonstrated that endotoxin 7 and thrombin 8 enhance synthesis of ET by endothelial cells. In clinical practice, plasma ET levels are significantly elevated in the patients with cirrhosis. 9 These studies raise the possibility that ET-1 may be involved in the pathogenesis of portal hypertension in various liver diseases.In regard to the regulatory mechanism along the anatomical pathway for the intrahepatic portal blood flow, the main site of resistance in the normal liver is an unsolved, controversial issue. Intrahepatic portal branches, hepatic sinusoids, and central veins, however, have been similarly suggested. 10 Intrahepatic portal system consists of conducting veins and distributing veins. 11 Conducting veins consist of interlobar veins, segmental veins, and interlobular veins with a diameter of larger than 300 to 400 mm. Distributing veins, which are characterized by the presence of inlet venules, include preterminal portal venules (PPV) and terminal portal venules, the latter of which are also termed septal branches. 12 By definition, PPV are the axial vessels of the complex acini and are localized at the corner of the liver lobule, and the terminal portal venules are the axial vessels of the simple acini. 11 Both vessels constitute the basic organization of the primary lobules as defined by Matsumoto et al. 12 This study was designed to reveal the major site of vascular constriction in the porto-sinusoidal system in response to ET-1 and resultant alterations of intrahepatic circulation. We used an in situ liver perfusion model with ET-1 at a constant flow rate to morphologically detect the intrahepatic heterogeneity of vasoconstrictive effects along the portal tree and the subsequent inhomogeneity of flow distribution under increased portal pressure.Abbreviations: ET-1, endothelin-1; PPV, preterminal portal venules; DS/PPV, distal segment of preterminal portal venules; PS/PPV, proximal segement of preterminal portal venules; KHB, Krebs-Henseleit buffer.From the

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“…In view of the potent pressor effects of ET-1, systemic hypertension was early recognized as target for ET antagonism [Schrader et al, 1990]. Moreover, circulating ET-1 concentration is elevated in patients with essential hypertension [Saito et al, 1990].…”

Section: Studies In Hypertensionmentioning

confidence: 99%

Darusentan, a selective endothelin A receptor antagonist, for the oral treatment of resistant hypertension

Enseleit¹,

Lüscher²,

Ruschitzka³

2010

Therapeutic Advances in Cardiovascular Disease

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Resistant hypertension is defined as failure to lower blood pressure to target when a patient adheres to the maximum tolerated doses of three antihypertensive drugs including a diuretic. Notwithstanding the wide availability of several antihypertensive agents and the continued recommendation of dietary and lifestyle modifications, the prevalence of resistant hypertension remains high and is expected to increase thus underscoring the need for potential new treatment modalities in resistant hypertension. Endothelin-1 is a long-lasting potent vasoconstrictor and plays a key role in cardiovascular haemostasis. Endothelin mediates its biological activity in humans through the endothelin A and B receptors. The clinical experience and the evidence for therapy with darusentan in resistant systemic hypertension are reviewed. The leading journals that publish basic science and clinical research in the area of cardiovascular diseases and PubMed were scanned. While results from early clinical studies suggested that darusentan might emerge as new treatment option in patients with resistant hypertension, results from recent studies suggests that darusentan appears unlikely to find its way in the armamentarium for treatment of resistant hypertension. AbstractBackground: Resistant hypertension is defined as failure to lower blood pressure to

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Plasma-Endothelin bei Normalpersonen und Patienten mit nephrologisch-rheumatologischen und kardiovaskulären Erkrankungen

Cited by 31 publications

References 28 publications

Evidence against a pathogenetic role for endothelin in pre‐eclampsia

Evidence against a pathogenetic role for endothelin in pre‐eclampsia

Endothelin-1-induced vasoconstriction causes a significant increase in portal pressure of rat liver: Localized constrictive effect on the distal segment of preterminal portal venules as revealed by light and electron microscopy and serial reconstruction

Darusentan, a selective endothelin A receptor antagonist, for the oral treatment of resistant hypertension

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