Titill: | Endothelium-derived hyperpolarizing factor (Edhf) mediates acetylsalicylic acid (aspirin) vasodilation of pregnant rat mesenteric arteries |
Höfundur: |
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Útgáfa: | 2021-09-21 |
Tungumál: | Enska |
Umfang: | 1878807 |
Deild: | Faculty of Pharmaceutical Sciences |
Birtist í: | International Journal of Molecular Sciences; 22(18) |
ISSN: | 1661-6596 |
DOI: | 10.3390/ijms221810162 |
Efnisorð: | Animals; Aspirin/therapeutic use; Biological Factors/genetics; Mesenteric Arteries/drug effects; Myocytes, Smooth Muscle/drug effects; Rats; Rats, Sprague-Dawley |
URI: | https://hdl.handle.net/20.500.11815/3263 |
Tilvitnun:Helgadóttir , H , Tropea , T , Gizurarson , S & Mandalà , M 2021 , ' Endothelium-derived hyperpolarizing factor (Edhf) mediates acetylsalicylic acid (aspirin) vasodilation of pregnant rat mesenteric arteries ' , International Journal of Molecular Sciences , vol. 22 , no. 18 , 10162 . https://doi.org/10.3390/ijms221810162
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Útdráttur:Acetylsalicylic acid (aspirin) exhibits a broad range of activities, including analgesic, antipyretic, and antiplatelet properties. Recent clinical studies also recommend aspirin prophylaxis in women with a high risk of pre-eclampsia, a major complication of pregnancy characterized by hypertension. We investigated the effect of aspirin on mesenteric resistance arteries and found out-discovered the molecular mechanism underlying this action. Aspirin (10−12–10−6 M) was tested on pregnant rat mesenteric resistance arteries by a pressurized arteriography. Aspirin was investigated in the presence of several inhibitors of: (a) nitric oxide synthase (L-NAME 2 × 10−4 M); (b) cyclooxygenase (Indomethacin, 10−5 M); (c) Ca2+-activated K+ channels (Kca): small conductance (SKca, Apamin, 10−7 M), intermediate conductance (IKca, TRAM34, 10−5 M), and big conductance (BKca, paxilline, 10−5 M); and (d) endothelial-derived hyperpolarizing factor (high KCl, 80 mM). Aspirin caused a concentration-dependent vasodilation. Aspirin-vasodilation was abolished by removal of endothelium or by high KCl. Furthermore, preincubation with either apamin plus TRAM-34 or paxillin significantly attenuated aspirin vasodilation (p < 0.05). For the first time, we showed that aspirin induced endothelium-dependent vasodilation in mesenteric resistance arteries through the endothelial-derived hyperpolarizing factor (EDHF) and calcium-activated potassium channels. By activating this molecular mechanism, aspirin may lower peripheral vascular resistance and be beneficial in pregnancies complicated by hypertension.
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Athugasemdir:Funding Information: Funding: This study was supported by the grants European Union 7th Framework Programme–FP7 (ASPRE Project # 601852); the Icelandic Research Fund (Rannís, no. 163369-051). Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).
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