{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T11:26:02Z","timestamp":1780485962501,"version":"3.54.1"},"reference-count":29,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Hypertension"],"published-print":{"date-parts":[[2003,9]]},"abstract":"<jats:p>\n            Deoxycorticosterone acetate (DOCA)\u2013salt hypertension is characterized by low renin\/angiotensin but increased arterial superoxide levels. We have recently reported that the arterial endothelin-1 (ET-1) level is increased, resulting in NADPH oxidase activation and superoxide generation. However, the effect of ET-1 on venous superoxide production and its relation to venoconstriction are unknown. The present study tested the hypotheses that ET-1 stimulates venous NADPH oxidase and superoxide via its ET\n            <jats:sub>A<\/jats:sub>\n            receptors, resulting in enhanced venoconstriction in DOCA-salt hypertensive rats. Treatment with ET-1 (0.01 to 1 nmol\/L), but not the selective ET\n            <jats:sub>B<\/jats:sub>\n            receptor agonist sarafotoxin s6c, of vena cavas of normal rats concentration-dependently increased superoxide levels, an effect that was abolished by the selective ET\n            <jats:sub>A<\/jats:sub>\n            receptor antagonist ABT-627. Although the ET-1 level was not increased in the vena cava and plasma, both venous NADPH oxidase activity and superoxide levels were significantly higher in DOCA-salt compared with sham rats. Moreover, ET-1 treatment (10\n            <jats:sup>\u22129<\/jats:sup>\n            mol\/L, 10 minutes) of isolated vena cavas further elevated superoxide levels in DOCA-salt rats only but not sham rats, an effect that was abrogated by the superoxide scavenger tempol. Similarly, ET-1\u2013induced contractions of isolated vena cavas of DOCA-salt but not sham rats were significantly inhibited by tempol. The NADPH oxidase inhibitor apocynin significantly reduced superoxide levels in vena cavas of DOCA-salt rats and in ET-1\u2013treated vena cavas of normal rats. Finally, in vivo ET\n            <jats:sub>A<\/jats:sub>\n            receptor blockade by ABT-627 significantly lowered venous superoxide levels and blood pressure in DOCA-salt but not sham rats. These results suggest that superoxide contributes to ET-1\u2013induced venoconstriction through an elevated venous NADPH oxidase activity in mineralocorticoid hypertension.\n          <\/jats:p>","DOI":"10.1161\/01.hyp.0000084853.47326.f2","type":"journal-article","created":{"date-parts":[[2003,7,29]],"date-time":"2003-07-29T00:38:17Z","timestamp":1059439097000},"page":"316-321","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":69,"title":["NADPH Oxidase\u2013Derived Superoxide Augments Endothelin-1\u2013Induced Venoconstriction in Mineralocorticoid Hypertension"],"prefix":"10.1161","volume":"42","author":[{"given":"Lixin","family":"Li","sequence":"first","affiliation":[{"name":"From the Department of Pharmacology and Toxicology and the Neuroscience Program, Michigan State University, East Lansing, Mich."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie W.","family":"Watts","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology and Toxicology and the Neuroscience Program, Michigan State University, East Lansing, Mich."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy K.","family":"Banes","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology and Toxicology and the Neuroscience Program, Michigan State University, East Lansing, Mich."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James J.","family":"Galligan","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology and Toxicology and the Neuroscience Program, Michigan State University, East Lansing, Mich."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory D.","family":"Fink","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology and Toxicology and the Neuroscience Program, Michigan State University, East Lansing, Mich."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex F.","family":"Chen","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology and Toxicology and the Neuroscience Program, Michigan State University, East Lansing, Mich."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jhh.1001034"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/hyp.32.1.59"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/hyp.37.1.77"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/hyp.31.1.139"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1995.75.3.611"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1097\/00005344-199012000-00012"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0741-5214(98)70061-8"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.95.3.588"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.101.14.1722"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/hyp.38.5.1107"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1097\/00004872-200104000-00011"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/atvb.22.2.249"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.0000051459.74466.46"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.hyp.0000047875.43777.79"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1161\/res.36.2.234807"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.hyp.21.3.294"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1161\/hyp.33.2.759"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00085.2002"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1097\/00004872-200204000-00024"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0704831"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.hyp.13.6.859"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.hyp.23.2.229"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1161\/res.89.4.357"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1748-1716.1981.tb06801.x"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.hyp.10.2.133"},{"key":"e_1_3_2_26_2","first-page":"3264","volume":"96","year":"1997","unstructured":"Griendling KK, Alexander RW. 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