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Endothelium-derived hyperpolarizing factor (Edhf) mediates acetylsalicylic acid (aspirin) vasodilation of pregnant rat mesenteric arteries

Endothelium-derived hyperpolarizing factor (Edhf) mediates acetylsalicylic acid (aspirin) vasodilation of pregnant rat mesenteric arteries


Title: Endothelium-derived hyperpolarizing factor (Edhf) mediates acetylsalicylic acid (aspirin) vasodilation of pregnant rat mesenteric arteries
Author: Helgadóttir, Helga
Tropea, Teresa   orcid.org/0000-0003-3972-3313
Gizurarson, Sveinbjörn
Mandalà, Maurizio   orcid.org/0000-0003-3736-0205
Date: 2021-09-21
Language: English
Scope:
Department: Faculty of Pharmaceutical Sciences
Series: International Journal of Molecular Sciences; 22(18)
ISSN: 1661-6596
DOI: https://doi.org/10.3390/ijms221810162
Subject: 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

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Citation:

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

Abstract:

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.

Description:

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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