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Regulation mechanisms of endocrine disruptors on vasodilation andvasoconstriction: Insights from ex vivo models

BIOCELL 2022年第6期46卷 1383-1389页

作者： MARGARIDA LORIGO elisa cairrao CICS-UBI Health Sciences Research CentreUniversity of Beira InteriorCovilhã6200-506Portugal FCS-UBI Faculty of Health SciencesUniversity of Beira InteriorCovilhã6200-506Portugal

Cardiovascular diseases (CVD) are one of the leading causes of death worldwide. The knowledge andunderstanding of CVD are based on the study of vascular physiology and how the smooth muscle cells and tissuesperform their different functions. Exposure to endocrine disruptors (EDCs), such as phytoestrogens, polycyclicaromatic hydrocarbons, flame retardants, plasticizers, pesticides, and cosmetics, is an integral and fundamental part ofhuman exposure. Humans are exposed to EDCs by multiple pathways including air, food, water, and consumerproducts. However, this exposure can lead to several adverse effects on human health, including on the cardiovascular(CV) system. The negative impact that EDC toxicity has on human CV health is a serious problem that must not beoverlooked. In this point of view, we proposed the use of the human umbilical artery as a human model to study thedirect effects of EDCs on the vascular level. Several works where these cells were directly exposed to EDC’s werepresented to highlight this well-established model as a great strategy to be used. In the future, we emphasize the needto continue to carry out different investigations using HUA to unveil and understand the vascular toxicity of EDCsand improve human CV health.

关键词： Vascular tonus Human umbilical artery Human exposome

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Study of the mechanisms regulating human umbilical artery contractility

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Health 2010年第4期2卷 321-331页

作者： António José Santos-Silva elisa cairrao Ignacio Verde Centro de Investigacao em Ciencias da Saude Universidade da Beira Interior Centro Hospitalar da Cova da Beira Quinta do Alvito

We studied the involvement of different types of Ca2+ channels, cyclic nucleotides and different kinases in the regulation of human umbilical artery (HUA) contractility. The elucidation of the precise mechanisms regulating the contractility of this artery could be very important to reveal potential therapeutic targets to treat HUA disorders such as preeclampsia. The relevancy of different types of Ca2+ channels on the regulation of HUA tonus was analyzed. Among the different Ca2+ channel inhibitors used, only the L-type calcium channels (LTCC) inhibition induced relaxation of HUA in Ca2+ containing medium. The inhibition of T-type calcium channels (TTCC) or TRP channels did not significantly affect HUA contractility. In presence of Ca2+, the intracellular increase of a cyclic nucleotide (cAMP or cGMP) induces relaxation of HUA, which was almost complete in histamine-con- tracted HUA, and lower effect was observed in arteries contracted by KCl and serotonin (5-HT). Inhibition of PKA and PKG weakly reduced the relaxations induced by the increase of cAMP and cGMP respectively, suggesting that the relaxation induced by these nucleotides is not totally mediated by the activation of their respective kinases and that other mechanisms are involved. In calcium containing solution, PP2A inhibition produces relaxation of contracted HUA. In KCl contracted arteries, the OA and nifedipine relaxant effects are similar and not additive, suggesting that PP2A could activate LTCC. Besides, the increase of cyclic nucleotides significantly increased the OA effect, suggesting that the effect of PP2A inhibition is independent of the cyclic nucleotide pathways. The contractions induced by KCl, histamine and 5-HT in presence of Ca2+ were not significantly affected by ROCK, ERK1/2 or p38MAPK inhibitors. In absence of extracellular Ca2+, histamine and 5-HT elicited contractions of HUA characterized by two components, a rapid phasic contractile component followed by a decrease of the contracti

关键词： Umbilical Artery Smooth Muscle L-type Ca2+ Channels ROCK Cyclic AMP Cyclic GMP

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Study of the mechanisms regulating human umbilical artery contractility

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Health 2010年第4期

作者： António José Santos-Silva elisa cairrao Ignacio Verde

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