{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T18:09:50Z","timestamp":1784225390895,"version":"3.55.0"},"reference-count":41,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2026,7,17]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>Endothelium-derived NO is an important vasodilator essential for maintaining vascular homeostasis. However, how eNOS (endothelial nitric oxide synthase) is regulated in hypertension conditions is not yet fully understood. In this study, we describe a critical role of the GLRA2 (\u03b12 subunit of glycine receptor) in modulating eNOS signaling and blood pressure regulation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>\n                      Endothelial-specific\n                      <jats:italic toggle=\"yes\">Glra2<\/jats:italic>\n                      -deficient mice and the adeno-associated viral-transfected mice were generated to assess the role of GLRA2 in hypertension models. Endothelium-dependent relaxation response and whole-cell patch clamp recording were determined.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>We first demonstrated selective expression of GLRA2 in arterial endothelial cells. Activation of GLRA2 by its ligand, glycine, effectively counteracts hypertension in a GLRA2-dependent manner. Our patient study indicated a negative correlation between plasma levels of glycine and blood pressure. Furthermore, we showed that endothelial GLRA2 regulates vasodilation by promoting NO production, rather than functioning solely as a chloride channel. Mechanistically, GLRA2 facilitates the phosphorylation of glycogen synthase kinase-3\u03b2 at Ser9 (serine 9), which activates the AKT (protein kinase B)\/eNOS signaling pathway in the endothelium, leading to increased NO release.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>This study discovers that a novel endothelial GLRA2 pathway holds significant potential for developing new strategies to control hypertension.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circresaha.126.328205","type":"journal-article","created":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T09:00:11Z","timestamp":1781859611000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Glycine Receptor \u03b12 Mediates Vasodilation via Endothelial eNOS Signaling"],"prefix":"10.1161","volume":"139","author":[{"given":"Xueya","family":"Bai","sequence":"first","affiliation":[{"name":"Department of Pathophysiology, Key Laboratory of Targeted Intervention of Cardiovascular Disease and Molecular Intervention (X.B., Y.W., W.Z., Y.Y., Y.D., J.L., H.B., Q.Y., B.J., J.B., H.Z., X.L., Xudong Zhu, Qi Chen), Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing Medical University, China."},{"name":"The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School (X.B., Xudong Zhu), Nanjing Medical University, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, Key Laboratory of Targeted Intervention of Cardiovascular Disease and Molecular Intervention (X.B., Y.W., W.Z., Y.Y., Y.D., J.L., H.B., Q.Y., B.J., J.B., H.Z., X.L., Xudong Zhu, Qi Chen), Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing Medical University, China."},{"name":"School of Medicine, Nanjing University of Chinese Medicine, China (Y.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9249-8939","authenticated-orcid":true,"given":"Wenying","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, Key Laboratory of Targeted Intervention of Cardiovascular Disease and Molecular Intervention (X.B., Y.W., W.Z., Y.Y., Y.D., J.L., H.B., Q.Y., B.J., J.B., H.Z., X.L., Xudong Zhu, Qi Chen), Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing Medical University, China."},{"name":"Department of Cardiology, Nanjing First Hospital Nanjing Medical University, China 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