Viswambharan, Hema Carvas, João Miguel Antic, Vladan Marecic, Ana Jud, Corinne Zaugg, Christian E. Ming, Xiu-Fen Montani, Jean-Pierre Albrecht, Urs Yang, Zhihong 2007-04-02 <i>Background—</i> The circadian clock regulates biological processes including cardiovascular function and metabolism. In the present study, we investigated the role of the circadian clock gene <i>Period2</i> (<i>Per2</i>) in endothelial function in a mouse model. <b><i>Methods and Results—</i></b> Compared with the wild-type littermates, mice with <i>Per2</i> mutation exhibited impaired endothelium-dependent relaxations to acetylcholine in aortic rings suspended in organ chambers. During transition from the inactive to active phase, this response was further increased in the wild-type mice but further decreased in the <i>Per2</i> mutants. The endothelial dysfunction in the <i>Per2</i> mutants was also observed with ionomycin, which was improved by the cyclooxygenase inhibitor indomethacin. No changes in the expression of endothelial acetylcholine-M₃ receptor or endothelial nitric oxide synthase protein but increased cyclooxygenase-1 (not cyclooxygenase-2) protein levels were observed in the aortas of the <i>Per2</i> mutants. Compared with <i>Per2</i> mutants, a greater endothelium-dependent relaxation to ATP was observed in the wild-type mice, which was reduced by indomethacin. In quiescent aortic rings, ATP caused greater endothelium-dependent contractions in the <i>Per2</i> mutants than in the wild-type mice, contractions that were abolished by indomethacin. The endothelial dysfunction in the <i>Per2</i> mutant mice is not associated with hypertension or dyslipidemia. <b><i>Conclusions—</i></b> Mutation in the <i>Per2</i> gene in mice is associated with aortic endothelial dysfunction involving decreased production of NO and vasodilatory prostaglandin(s) and increased release of cyclooxygenase-1–derived vasoconstrictor(s). The results suggest an important role of the <i>Per2</i> gene in maintenance of normal cardiovascular functions. application/pdf https://folia.unifr.ch/global/documents/300364 https://folia.unifr.ch/documents/300364/files/yang_mcc.pdf https://folia.unifr.ch/documents/300364/files/yang_mcc_su.pdf eng info:eu-repo/semantics/altIdentifier/doi/10.1161/CIRCULATIONAHA.106.653303 info:eu-repo/semantics/openAccess License undefined Circulation. - 2007, vol. 115, p. 2188-2195 acetylcholine circadian rhythm cyclooxygenase 1 endothelium nitricoxide vasodilation info:eu-repo/classification/udc/57 Mutation of the circadian clock gene Per2 alters vascular endothelial function http://purl.org/coar/resource_type/c_6501