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- Luksha, LKarolinska Institutet (author)
Endothelium-derived hyperpolarizing factor in preeclampsia: heterogeneous contribution, mechanisms, and morphological prerequisites
- Article/chapterEnglish2008
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- American Physiological Society,2008
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- LIBRIS-ID:oai:prod.swepub.kib.ki.se:116479746
- http://kipublications.ki.se/Default.aspx?queryparsed=id:116479746URI
- https://doi.org/10.1152/ajpregu.00458.2007DOI
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- Language:English
- Summary in:English
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- We hypothesized that in preeclampsia (PE), contribution of endothelium-derived hyperpolarizing factor (EDHF) and the mechanism/s of its action differ from that in normal pregnancy (NP). We aimed to assess endothelial function and morphology in arteries from NP and PE with particular focus on EDHF. Arteries (≈200 μm) were dissected from subcutaneous fat biopsies obtained from women undergoing cesarean section. With the use of wire myography, responses to the endothelium-dependent agonist bradykinin (BK) were determined before and after inhibition of pathways relevant to EDHF activity. The overall responses to BK in arteries from PE ( n = 13) and NP ( n = 17) were similar. However, in PE, EDHF-mediated relaxation was reduced ( P < 0.05). All women within the PE group were divided into two subgroups: with more ( group 1) or less ( group 2) than 50% reduction of EDHF-typed responses after 18-α-glycyrrhetinic acid (an inhibitor of myoendothelial gap junctions, MEGJs). The division showed that 1) MEGJs are principally involved when the EDHF contribution is reduced; and 2) when the EDHF contribution is similar to that in NP, the H2O2 and/or cytochrome P-450 epoxygenase products of arachidonic acid (AA), along with MEGJs, confer EDHF-mediated relaxation. In contrast, MEGJs were the main pathway for EDHF in NP. The abundant presence of MEGJs in arteries from NP but deficiency of them in PE was observed using transmission electron microscopy. We conclude that PE is associated with heterogeneous contribution of EDHF, and the mechanism behind EDHF-typed responses is mediated either by MEGJs alone or in combination with H2O2 or cytochrome P-450 epoxygenase metabolites of AA.
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- Nisell, HKarolinska Institutet (author)
- Luksha, NKarolinska Institutet (author)
- Kublickas, MKarolinska Institutet (author)
- Hultenby, KKarolinska Institutet (author)
- Kublickiene, KKarolinska Institutet (author)
- Karolinska Institutet (creator_code:org_t)
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- In:American journal of physiology. Regulatory, integrative and comparative physiology: American Physiological Society294:2, s. R510-R5190363-61191522-1490
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