García-Redondo, Ana BEsteban, VanesaBriones, Ana MDíaz Del Campo, Lucía SGonzález-Amor, MaríaMendez-Barbero, NereaCampanero, Miguel RRedondo, Juan MiguelSalaices, Mercedes2020-04-302020-04-302018-07Pharmacol Res. 2018; 133:236-24910436618http://hdl.handle.net/20.500.12105/9847Cyclooxygenase-2 (COX-2) derived-prostanoids participate in the altered vascular function and mechanical properties in cardiovascular diseases. We investigated whether regulator of calcineurin 1 (Rcan1) participates in vascular contractility and stiffness through the regulation of COX-2. For this, wild type (Rcan1+/+) and Rcan1-deficient (Rcan1-/-) mice untreated or treated with the COX-2 inhibitor rofecoxib were used. Vascular function and structure were analysed by myography. COX-2 and phospo-p65 expression were studied by western blotting and immunohistochemistry and TXA2 production by ELISA. We found that Rcan1 deficiency increases COX-2 and IL-6 expression and NF-κB activation in arteries and vascular smooth muscle cells (VSMC). Adenoviral-mediated re-expression of Rcan1.4 in Rcan1-/- VSMC normalized COX-2 expression. Phenylephrine-induced vasoconstrictor responses were greater in aorta from Rcan1-/- compared to Rcan1+/+ mice. This increased response were diminished by etoricoxib, furegrelate, SQ 29548, cyclosporine A and parthenolide, inhibitors of COX-2, TXA2 synthase, TP receptors, calcineurin and NF-κB, respectively. Endothelial removal and NOS inhibition increased phenylephrine responses only in Rcan1+/+ mice. TXA2 levels were greater in Rcan1-/- mice. In small mesenteric arteries, vascular function and structure were similar in both groups of mice; however, vessels from Rcan1-/- mice displayed an increase in vascular stiffness that was diminished by rofecoxib. In conclusion, our results suggest that Rcan1 might act as endogenous negative modulator of COX-2 expression and activity by inhibiting calcineurin and NF-kB pathways to maintain normal contractility and vascular stiffness in aorta and small mesenteric arteries, respectively. Our results uncover a new role for Rcan1 in vascular contractility and mechanical properties.engAMhttp://creativecommons.org/licenses/by-nc-nd/4.0/COX-2Rcan1Vascular function and stiffnessAnimalsAorta, ThoracicCalcium-Binding ProteinsCells, CulturedCyclooxygenase 2Attribution-NonCommercial-NoDerivatives 4.0 Internacional29309904133236-24910.1016/j.phrs.2018.01.0011096-1186Pharmacological researchopen access