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Association of circulating endothelin and noradrenaline with increased calcium-channel binding sites in the placental bed in pre-eclampsia

Title
Association of circulating endothelin and noradrenaline with increased calcium-channel binding sites in the placental bed in pre-eclampsia
Type
Article in International Scientific Journal
Year
1998
Authors
Ferreira de Almeida, JA
(Author)
Other
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Amenta, F
(Author)
Other
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Cardoso, F
(Author)
Other
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Polonia, JJ
(Author)
FMUP
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Journal
Vol. 105
Pages: 1104-1112
ISSN: 1470-0328
Publisher: Wiley-Blackwell
Scientific classification
FOS: Medical and Health sciences > Clinical medicine
Other information
Authenticus ID: P-001-6YV
Abstract (EN): Objective To evaluate factors contributing to both placental hypoperfusion and maternal vasoconstriction in pre-eclampsia. Design Single centre, comparative study of calcium-channel density and affinity in the placental bed of pregnant women with normotension and pre-eclampsia. Setting Teaching hospital. Participants Twenty-two primigravidae in the third trimester of pregnancy: 10 with pre-eclampsia and 12 normotensive. Methods Plasma levels of endothelin-1 (by RIA) and noradrenaline (by HPLC-ED) were measured. Both pharmacological characterisation and anatomical localisation of dihydropyridine-sensitive binding sites (using radioligand-binding studies and autorradiographic techniques) were determined with 3H-isradipine in placental bed tissues to determine both the density (Bmax) and the affinity (Kd) of receptor sites. Results Higher plasma levels of endothelin-1 and noradrenalin were found in women with preeclampsia compared with normotensive women. Placental bed tissues bound 3H-isradipine in a saturable, reversible time and temperature-dependent manner with very low Kd values. Study of the 3H-isradipine specificity binding included the use of several dihydropyridine displacers. In the group with pre-eclampsia the Scatchard analysis of the results showed a significant increase (P < 0.001) both in the affinity [Kd = 0.23 nmol (0.04) vs 0 45 nmol (0.03), pre-eclampsia vs normotensive] and in the density of calcium-channel binding sites [Bmax = 77.70 fmol/mg (1.30) vs 64.30 fmol/mg (1.80) tissue, pre-eclampsia vs normotensive]. Autoradiography confirmed that in the placental bed tissue of those with pre-eclampsia there was a much higher silver grain density in the arteries walls, compared with normotensive women. Conclusions In pre-eclampsia there is an increase in the maternal circulation of two strong vasoconstrictor factors (endothelin-1 and noradrenalin) and a sharp increase both in the density and the affinity of calcium-channel binding sites in placental bed central area. The latter may strongly contribute to the perpetuation of the uteroplacental hypoperfusion either by itself or by amplifying the local actions of circulating factors, such as endothelin-l and noradrenalin.
Language: English
Type (Professor's evaluation): Scientific
No. of pages: 9
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