{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T22:19:04Z","timestamp":1792880344483,"version":"4.5.0"},"reference-count":70,"publisher":"American Physiological Society","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2013,11,15]]},"abstract":"<jats:p>Regulation of blood pressure by angiotensin II (ANG II) is a process that involves the reactive oxygen species (ROS) and calcium. We have shown that ANG-II type 1 receptor (AT<jats:sub>1<\/jats:sub>R) and prostaglandin E<jats:sub>2<\/jats:sub>(PGE<jats:sub>2<\/jats:sub>) type 1 receptors (EP<jats:sub>1<\/jats:sub>R) are required in the subfornical organ (SFO) for ROS-mediated hypertension induced by slow-pressor ANG-II infusion. However, the signaling pathway associated with this process remains unclear. We sought to determine mechanisms underlying the ANG II-induced ROS and calcium influx in mouse SFO cells. Ultrastructural studies showed that cyclooxygenase 1 (COX-1) codistributes with AT<jats:sub>1<\/jats:sub>R in the SFO, indicating spatial proximity. Functional studies using SFO cells revealed that ANG II potentiated PGE<jats:sub>2<\/jats:sub>release, an effect dependent on AT<jats:sub>1<\/jats:sub>R, phospholipase A<jats:sub>2<\/jats:sub>(PLA<jats:sub>2<\/jats:sub>) and COX-1. Furthermore, both ANG II and PGE<jats:sub>2<\/jats:sub>increased ROS formation. While the increase in ROS initiated by ANG II, but not PGE<jats:sub>2<\/jats:sub>, required the activation of the AT<jats:sub>1<\/jats:sub>R\/PLA<jats:sub>2<\/jats:sub>\/COX-1 pathway, both ANG II and PGE<jats:sub>2<\/jats:sub>were dependent on EP<jats:sub>1<\/jats:sub>R and Nox2 as downstream effectors. Finally, ANG II potentiated voltage-gated L-type Ca<jats:sup>2+<\/jats:sup>currents in SFO neurons via the same signaling pathway required for PGE<jats:sub>2<\/jats:sub>production. Blockade of EP<jats:sub>1<\/jats:sub>R and Nox2-derived ROS inhibited ANG II and PGE<jats:sub>2<\/jats:sub>-mediated Ca<jats:sup>2+<\/jats:sup>currents. We propose a mechanism whereby ANG II increases COX-1-derived PGE<jats:sub>2<\/jats:sub>through the AT<jats:sub>1<\/jats:sub>R\/PLA<jats:sub>2<\/jats:sub>pathway, which promotes ROS production by EP<jats:sub>1<\/jats:sub>R\/Nox2 signaling in the SFO. ANG II-induced ROS are coupled with Ca<jats:sup>2+<\/jats:sup>influx in SFO neurons, which may influence SFO-mediated sympathoexcitation. Our findings provide the first evidence of a spatial and functional framework that underlies ANG-II signaling in the SFO and reveal novel targets for antihypertensive therapies.<\/jats:p>","DOI":"10.1152\/ajpheart.00238.2013","type":"journal-article","created":{"date-parts":[[2013,9,7]],"date-time":"2013-09-07T05:34:53Z","timestamp":1378532093000},"page":"H1451-H1461","source":"Crossref","is-referenced-by-count":33,"title":["COX-1-derived PGE<sub>2<\/sub>and PGE<sub>2<\/sub>type 1 receptors are vital for angiotensin II-induced formation of reactive oxygen species and Ca<sup>2+<\/sup>influx in the subfornical organ"],"prefix":"10.1152","volume":"305","author":[{"given":"Gang","family":"Wang","sequence":"first","affiliation":[{"name":"The Brain and Mind Research Institute, Weill Cornell Medical College, New York, New York;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pallabi","family":"Sarkar","sequence":"additional","affiliation":[{"name":"Department of Cell and 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