Enhancement by Hydrogen Peroxide of Calcium Signals in Endothelial Cells Induced by 5-HT1B and 5-HT2B Receptor Agonists

Abstract

Hydrogen peroxide, formed in the endothelium, acts as a factor contributing to the relaxation of blood vessels. The reason for this vasodilatory effect could be modulation by H2O2 of calcium metabolism, since mobilization of calcium ions in endothelial cells is a trigger of endothelium-dependent relaxation. The aim of this work was to investigate the influence of H2O2 on the effects of Ca2+-mobilizing agonists in human umbilical vein endothelial cells (HUVEC). We have found that H2O2 in concentration range 10-100 μM increases the rise of [Ca2+]i induced by 5-hydroxytryptamine (5-HT) and carbachol and does not affect the calcium signals of ATP, agonist of type 1 protease-activated receptor SFLLRN, histamine and bradykinin. Using specific agonists of 5-HT1B and 5-HT2B receptors CGS12066B and BW723C86, we have demonstrated that H2O2 potentiates the effects mediated by these types of 5-HT receptors. Potentiation of the effect of BW723C86 can be produced by the induction of endogenous oxidative stress in HUVEC. We have shown that the activation of 5-HT2B receptor by BW723C86 causes production of reactive oxygen species (ROS). Inhibitor of NADPH oxidases VAS2870 suppressed formation of ROS and partially inhibited [Ca2+]i rise induced by BW723C86. Thus, it can be assumed that vasorelaxation induced by endogenous H2O2 in endothelial cells partially occurs due to the potentiation of the agonist-induced calcium signaling.

Aquaporin 8 is involved in H2O2‐mediated differential regulation of metabolic signaling by α1‐ and β‐adrenoceptors in hepatocytes

“…In contrast, adrenaline‐stimulated β‐AR increases metabolic pathways, which were inhibited by H 2 O 2 either by α 1 ‐AR activation [5] or by addition of the ROS, that is, blockade of AQP8 by antibodies avoided H 2 O 2 ‐induced inhibition of β‐AR effects and confirmed AQP8’s role in the signaling (this work). In addition, it has been reported that H 2 O 2 (100 µ m ) induces Ca 2+ increase in endothelial cells due to 5‐HT1 receptor activation, increase that is similar to the one we found here [50].…”

NADPH oxidase in the vasculature: Expression, regulation and signalling pathways; role in normal cardiovascular physiology and its dysregulation in hypertension

“…As in VSM, NOX isoforms 1, 2, 4 and 5 are all expressed in the vascular endothelium[53,54,215,234,[413][414][415] and are likely sources of the ROS contributing to or influencing these relaxation responses. Indeed, acetylcholine, histamine, bradykinin and flow all induce NOX-derived ROS production in vascular tissues and cultured endothelial cells[237,402,405,408,414,[416][417][418][418][419][420][421] (Table1). Vascular relaxation responses in isolated arteries and cerebral blood flow are improved by non-selective NOX inhibitors…”

The Use of Fluorescently Labeled ARC1779 Aptamer for Assessing the Effect of H2O2 on von Willebrand Factor Exocytosis

“…H 2 O 2 acts as a sec ond messenger by inhibiting protein tyrosine phos phatases [37]. In ECs, H 2 O 2 selectively promotes the effect of agonists of 5 HT1B and 5 HT2B receptors [38] and stimulates two pore endolysosomal calcium channels [39]. The data on the effect of H 2 O 2 on vWF secretion are quite contradictory.…”