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 H(2)O(2) 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 H(2)O(2) on the effects of Ca(2+)-mobilizing agonists in human umbilical vein endothelial cells (HUVEC). We have found that H(2)O(2) in concentration range 10-100 μM increases the rise of [Ca(2+)](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 H(2)O(2) 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 [Ca(2+)](i) rise induced by BW723C86. Thus, it can be assumed that vasorelaxation induced by endogenous H(2)O(2) in endothelial cells partially occurs due to the potentiation of the agonist-induced calcium signaling.