{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T11:02:06Z","timestamp":1790938926340,"version":"4.1.0"},"reference-count":23,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Hypertension"],"published-print":{"date-parts":[[1999,12]]},"abstract":"<jats:p>\n            <jats:italic>Abstract<\/jats:italic>\n            \u2014The effects of hypoxanthine and xanthine oxidase\u2013induced superoxide anion were evaluated on various signal transduction pathways in aortic smooth muscle cells (SMCs) from spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). Superoxide increased inositol 1,4,5-tris-phosphate (IP\n            <jats:sub>3<\/jats:sub>\n            ) formation in a concentration- and time-dependent manner in both strains but more markedly in SMCs from SHR. Various antioxidants significantly decreased the superoxide-induced IP\n            <jats:sub>3<\/jats:sub>\n            formation in both strains. In addition, tyrosine kinase inhibitors, genistein and tyrphostin A25, inhibited the superoxide-induced IP\n            <jats:sub>3<\/jats:sub>\n            formation more markedly in SHR than in WKY. Moreover, superoxide decreased the basal level of cGMP to a greater extent in SHR and also suppressed the rise in cGMP induced by\n            <jats:italic>S<\/jats:italic>\n            -nitroso-\n            <jats:italic>N<\/jats:italic>\n            -acetylpenicillamine. In addition, the superoxide-induced increase in IP\n            <jats:sub>3<\/jats:sub>\n            formation was significantly inhibited by guanylyl cyclase stimulator\n            <jats:italic>S<\/jats:italic>\n            -nitroso-\n            <jats:italic>N<\/jats:italic>\n            -acetylpenicillamine but was potentiated by ODQ (a guanylyl cyclase inhibitor, 1\n            <jats:italic>H<\/jats:italic>\n            -[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one) and KT5823 (a cGMP-dependent protein kinase inhibitor), with a greater effect in SHR. Finally, the superoxide-enhanced IP\n            <jats:sub>3<\/jats:sub>\n            formation was not accompanied by simultaneous changes in cAMP levels, and inhibition of the adenylyl cyclase pathway did not modify the superoxide-induced IP\n            <jats:sub>3<\/jats:sub>\n            formation. Our results thus demonstrate a stimulatory effect of superoxide on IP\n            <jats:sub>3<\/jats:sub>\n            formation, mediated by the tyrosine kinase\u2013coupled phospholipase C\n            <jats:sub>\u03b3<\/jats:sub>\n            activity, and an inhibitory effect of superoxide on cGMP formation in vascular SMCs. The increased reactivity of the phospholipase C pathway and the decreased cross inhibition of the IP\n            <jats:sub>3<\/jats:sub>\n            pathway by cGMP in the presence of superoxide may underlie the altered functions of vascular SMCs in SHR.\n          <\/jats:p>","DOI":"10.1161\/01.hyp.34.6.1247","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T00:53:46Z","timestamp":1339462426000},"page":"1247-1253","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":30,"title":["Effects of Superoxide on Signaling Pathways in Smooth Muscle Cells From Rats"],"prefix":"10.1161","volume":"34","author":[{"given":"Lingyun","family":"Wu","sequence":"first","affiliation":[{"name":"From the Groupe de Recherche sur le Syste\u0300me Nerveux Autonome, Faculty of Medicine, Universite\u0301 de Montre\u0301al, Montreal, Quebec, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacques","family":"de Champlain","sequence":"additional","affiliation":[{"name":"From the Groupe de Recherche sur le Syste\u0300me Nerveux Autonome, Faculty of Medicine, Universite\u0301 de Montre\u0301al, Montreal, Quebec, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1161\/res.81.4.550"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1997.272.5.C1558"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)50453-7"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)42284-3"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1411571"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1097\/00004872-199816030-00011"},{"key":"e_1_3_2_7_2","first-page":"239","volume":"259","year":"1997","unstructured":"Wu L, de Champlain J. Superoxide anion-induced formation of inositol phosphates involves tyrosine kinase activity in smooth muscle cells from rat mesenteric arteries. Biochem Biophys Res Commun. 1997;259:239\u2013243.","journal-title":"Biochem Biophys Res Commun"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1991.tb12166.x"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1097\/00004872-199605000-00008"},{"key":"e_1_3_2_10_2","first-page":"810","volume":"63","year":"1998","unstructured":"Wolin MS, Davidson CA, Kaminski PM, Fayngersh RP, Mohazzab-H KM. Oxidant\u2013nitric oxide signalling mechanisms in vascular tissue. Biochemistry. 1998;63:810\u2013816.","journal-title":"Biochemistry"},{"key":"e_1_3_2_11_2","first-page":"H1056","volume":"259","year":"1990","unstructured":"Cherry PD, Omar HA, Farrell KA, Stuart JS, Wolin MS. Superoxide anion inhibits cGMP-associated bovine pulmonary arterial relaxation. Am J Physiol. 1990;259:H1056\u2013H1062.","journal-title":"Am J Physiol"},{"key":"e_1_3_2_12_2","first-page":"A325","volume":"9","year":"1995","unstructured":"Mesaros S, Grunfeld S, Bohr DF, Malinski T. Nitric oxide and superoxide in heart and aorta from normotensive (WKY) and hypertensive (SHRSP) rats. FASEB J. 1995;9:A325. Abstract.","journal-title":"FASEB J"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.hyp.13.6.859"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0891-5849(96)00275-4"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1161\/hyp.25.2.155"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.3.1711"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.16.9052"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.hyp.23.4.476"},{"key":"e_1_3_2_19_2","first-page":"75","volume":"327","year":"1997","unstructured":"Kawada T, Toyosato A, Islam O, Yoshida Y, Imai S. cGMP-kinase mediates cGMP- and cAMP-induced Ca2+ desensitization of skinned rat artery. Eur J Pharmacol. 1997;327:75\u201382.","journal-title":"Eur J Pharmacol"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0701222"},{"key":"e_1_3_2_21_2","unstructured":"Opie LH. Vascular smooth muscle and endothelium. The Heart Physiology From Cell to Circulation. 3rd ed. Philadelphia Pa: Lippincott-Raven; 1998:233\u2013264."},{"key":"e_1_3_2_22_2","unstructured":"Bennett BM Waldman SA. Cyclic nucleotides and protein phosphorylation in vascular smooth muscle relaxation. In: Sperelakis N ed. Physiology and Pathophysiology of the Heart. 3rd ed. Boston Mass: Kluwer Academic Publishers; 1995:975\u2013998."},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)48388-3"}],"container-title":["Hypertension"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/01.HYP.34.6.1247","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,12]],"date-time":"2024-05-12T17:48:24Z","timestamp":1715536104000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/01.HYP.34.6.1247"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1999,12]]},"references-count":23,"journal-issue":{"issue":"6","published-print":{"date-parts":[[1999,12]]}},"alternative-id":["10.1161\/01.HYP.34.6.1247"],"URL":"https:\/\/doi.org\/10.1161\/01.hyp.34.6.1247","relation":{},"ISSN":["0194-911X","1524-4563"],"issn-type":[{"value":"0194-911X","type":"print"},{"value":"1524-4563","type":"electronic"}],"subject":[],"published":{"date-parts":[[1999,12]]},"assertion":[{"value":"1999-04-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"1999-07-30","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"1999-12-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}