{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T18:22:24Z","timestamp":1790446944205,"version":"4.1.0"},"reference-count":58,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2025,1,21]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Prostaglandin E\n              <jats:sub>2<\/jats:sub>\n              (PGE\n              <jats:sub>2<\/jats:sub>\n              ) in the rostral ventrolateral medulla (RVLM) has been recognized as a pivotal pressor substance in hypertension, yet understanding of its effects and origins in the RVLM remains largely elusive. This study aimed to elucidate the pivotal enzymes and molecular mechanisms underlying PGE\n              <jats:sub>2<\/jats:sub>\n              synthesis induced by central Ang II (angiotensin II) and its implications in the heightened oxidative stress and sympathetic outflow in hypertension.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              RVLM microinjections of PGE\n              <jats:sub>2<\/jats:sub>\n              and Tempol were administered in Wistar\u2010Kyoto rats. Intracisternal drug delivery and adeno\u2010associated viral vectors microinjection were used in both Wistar\u2010Kyoto rats and spontaneous hypertensive rats to modulate the function of Ang II, PGE\n              <jats:sub>2<\/jats:sub>\n              receptor 3, and expression of COX2 (cyclooxygenase 2). Microinjection of PGE\n              <jats:sub>2<\/jats:sub>\n              into the RVLM significantly augmented sympathetic activity (25.380\u00b11.566%) and oxidative stress level, whereas intracisternal infusion of a prostaglandin E receptor 3 antagonist attenuated sympathetic activity in both spontaneous hypertensive rats and Ang II\u2010induced hypertensive rats. Furthermore, Ang II treatment upregulated COX2 expression in RVLM neurons (1.000\u00b10.112 versus 1.506\u00b10.370 fold change), with no significant effect on other enzymes involved in PGE\n              <jats:sub>2<\/jats:sub>\n              synthesis. Additionally, inhibition of the JAK2\/STAT3 (Janus kinase 2\/signal transducer and activator of transcription 3) signaling pathway nullified Ang II\u2010mediated elevation of COX2 expression, as evidenced by phosphorylated STAT3 binding to the COX2 sequence in PC12 cells.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Central Ang II induces the accumulation of RVLM PGE\n              <jats:sub>2<\/jats:sub>\n              through the neuronal AT1R (angiotensin type 1 receptor)\/JAK2\/STAT3\/COX2 pathway, thereby promoting oxidative stress, augmenting sympathetic outflow, and contributing to essential hypertension.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.124.036762","type":"journal-article","created":{"date-parts":[[2025,1,16]],"date-time":"2025-01-16T11:55:00Z","timestamp":1737028500000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":10,"title":["Janus Kinase 2\/Signal Transducer and Activator of Transcription 3\/Cyclooxygenase 2 Signaling Pathway Mediates the Effect of Central Angiotensin II on the Elevation of Rostral Ventrolateral Medulla Prostaglandin E\n            <sub>2<\/sub>\n            \u2010Induced Oxidative Stress in Hypertension"],"prefix":"10.1161","volume":"14","author":[{"given":"Jie\u2010Fu","family":"Fan","sequence":"first","affiliation":[{"name":"Naval Medical Center of PLA Naval Medical University (Second Military Medical University) Shanghai 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