Human umbilical artery smooth muscle exhibits a 2-APBsensitive capacitative contractile response evoked by vasoactive substances and expresses mRNAs for STIM, Orai and TRPC channels

After depletion of intracellular Ca^(2+)stores the capacitative response triggers an extracellular Ca^(2+)influx through store-operated channels(SOCs)which refills these stores.Our objective was to explore if human umbilical artery smooth muscle presented this response and if it was involved in the mechanism of serotonin-and histamine-induced contractions.Intracellular Ca^(2+)depletion by a Ca^(2+)-free extracellular solution followed by Ca^(2+)readdition produced a contraction in artery rings which was inhibited by the blocker of Orai and TRPC channels 2-aminoethoxydiphenyl borate(2-APB),suggesting a capacitative response.In presence of 2-APB the magnitude of a second paired contraction by serotonin or histamine was significantly less than a first one,likely because 2-APB inhibited store refilling by capacitative Ca^(2+)entry.2-APB inhibition of sarcoplasmic reticulum Ca^(2+)release was excluded because this blocker did not affect serotonin force development in a Ca^(2+)-free solution.The PCR technique showed the presence of mRNAs for STIM proteins(1 and 2),for Orai proteins(1,2 and 3)and for TRPC channels(subtypes 1,3,4 and 6)in the smooth muscle of the human umbilical artery.Hence,this artery presents a capacitative contractile response triggered by stimulation with physiological vasoconstrictors and expresses mRNAs for proteins and channels previously identified as SOCs.

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

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.