| 1. |
- Luksha, L, et al.
(författare)
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Endothelium-derived hyperpolarizing factor in preeclampsia: heterogeneous contribution, mechanisms, and morphological prerequisites
- 2008
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Ingår i: American journal of physiology. Regulatory, integrative and comparative physiology. - : American Physiological Society. - 0363-6119 .- 1522-1490. ; 294:2, s. R510-R519
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Tidskriftsartikel (refereegranskat)abstract
- 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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| 2. |
- Luksha, L, et al.
(författare)
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The mechanism of EDHF-mediated responses in subcutaneous small arteries from healthy pregnant women
- 2004
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Ingår i: American journal of physiology. Regulatory, integrative and comparative physiology. - : American Physiological Society. - 0363-6119 .- 1522-1490. ; 286:6, s. R1102-R1109
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Tidskriftsartikel (refereegranskat)abstract
- We studied the importance of endothelium-derived hyperpolarizing factor (EDHF) vs. nitric oxide (NO) and prostacyclin (PGI2) in bradykinin (BK)-induced relaxation in isolated small subcutaneous arteries from normal pregnant women. We also explored the contribution of cytochrome P-450 (CYP450) product of arachidonic acid (AA) metabolism, hydrogen peroxide (H2O2), and gap junctions that have been suggested to be involved in EDHF-mediated responses. Isolated arteries obtained from subcutaneous fat biopsies of normal pregnant women ( n = 30) undergoing planned cesarean section were mounted in a wire-myography system. In norepinephrine-constricted vessels, incubation with NG-nitro-l-arginine methyl ester (l-NAME) resulted in a significant reduction in relaxation to BK. Simultaneous incubation with l-NAME and indomethacin failed to modify this response further. BK-mediated dilatation in the presence of K+-modified solution was decreased to similar level as obtained after incubation with l-NAME. Incubation with l-NAME abolished BK-induced responses in K+-modified solution. Sulfaphenazole, a specific inhibitor of CYP450 epoxygenase, and catalase (an enzyme that decomposes H2O2) did not affect the EDHF-mediated relaxation because concentration-response curves to BK were similar in arteries after incubation with l-NAME vs. l-NAME + sulfaphenazole and l-NAME + catalase. The inhibitor of gap junctions, 18α-glycyrrhetinic acid, significantly reduced BK-mediated relaxation both without and with incubation with l-NAME. We found that both NO and EDHF, but not PGI2, are involved in the endothelium-dependent dilatation to BK. BK-induced relaxation is almost equally mediated by NO and EDHF. CYP450 epoxygenase metabolites of AA or H2O2 do not account for EDHF-mediated response; however, gap junctions are involved in the EDHF-mediated responses to BK in subcutaneous small arteries in normal pregnancy.
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