{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T19:33:32Z","timestamp":1790883212623,"version":"4.1.0"},"reference-count":47,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2000,2,1]],"date-time":"2000-02-01T00:00:00Z","timestamp":949363200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["HL59791"],"award-info":[{"award-number":["HL59791"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HL63067"],"award-info":[{"award-number":["HL63067"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2000,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Angiotensin II (ANG II) is a well\u2010established participant in many cardiovascular disorders, but the mechanisms involved are not clear. Vascular cell experiments suggest that ANG II is a potent stimulator of free radicals such as superoxide anion, an agent known to inactivate nitric oxide and promote the formation of peroxynitrite. Here we hypothesized that ANG II reduces the efficacy of NO\u2010mediated vascular relaxation and promotes vascular peroxynitrite formation\n                    <jats:italic>in vivo<\/jats:italic>\n                    . ANG II was infused in rats at sub\u2010pressor doses for 3 days. Systolic blood pressure and heart rate were unchanged on day 3 despite significant reductions in plasma renin activity. Thoracic aorta was isolated for functional and immunohistochemical evaluations. No difference in isolated vascular contractile responses to KCI (125 mM), phenylephrine, or ANG II was observed between groups. In contrast, relaxant response to acetylcholine (ACh) was decreased sixfold without a change in relaxant response to sodium nitroprusside. Extensive prevalence of 3\u2010nitrotyrosine (3\u2010NT, a stable biomarker of tissue peroxynitrite formation) immunoreactivity was observed in ANG II\u2010treated vascular tissues and was specifically confined to the endothelium. Digital image analysis demonstrated a significant inverse correlation between ACh relaxant response and 3\u2010NT immunoreactivity. These data demonstrate that ANG II selectively modifies vascular NO control at sub\u2010pressor exposures\n                    <jats:italic>in vivo<\/jats:italic>\n                    . Thus, endothelial dysfunction apparently precedes other established ANG II\u2010induced vascular pathologies, and this may be mediated by peroxynitrite formation\n                    <jats:italic>in vivo<\/jats:italic>\n                    . Wattanapitayakul, S., Weinstein, D. M., Holycross, B. J., Bauer, J. A. Endothelial dysfunction and peroxynitrite formation are early events in angiotensin\u2010induced cardiovascular disorders.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    14, 271\u2013278 (2000)\n                  <\/jats:p>","DOI":"10.1096\/fasebj.14.2.271","type":"journal-article","created":{"date-parts":[[2018,1,18]],"date-time":"2018-01-18T08:55:58Z","timestamp":1516265758000},"page":"271-278","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":132,"title":["Endothelial dysfunction and peroxynitrite formation are early events in angiotensin\u2010induced cardiovascular disorders"],"prefix":"10.1096","volume":"14","author":[{"given":"Suvara Kimnite","family":"Wattanapitayakul","sequence":"first","affiliation":[{"name":"Division of Pharmacology College of Pharmacy The Ohio State University  Columbus Ohio 43210 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M.","family":"Weinstein","sequence":"additional","affiliation":[{"name":"Division of Pharmacology College of Pharmacy The Ohio State University  Columbus Ohio 43210 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bethany J.","family":"Holycross","sequence":"additional","affiliation":[{"name":"Division of Pharmacology College of Pharmacy The Ohio State University  Columbus Ohio 43210 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John Anthony","family":"Bauer","sequence":"additional","affiliation":[{"name":"Division of Pharmacology College of Pharmacy The Ohio State University  Columbus Ohio 43210 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2000,2]]},"reference":[{"issue":"1","key":"e_1_2_6_2_1","doi-asserted-by":"crossref","first-page":"S21","DOI":"10.1097\/00005344-199900001-00005","article-title":"The renin\u2010angiotensin system and its receptors","volume":"33","author":"Stroth U.","year":"1999","journal-title":"J. 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