{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T09:49:09Z","timestamp":1779184149429,"version":"3.51.4"},"reference-count":35,"publisher":"American Physiological Society","issue":"9","funder":[{"name":"National Institute of Health, USA","award":["NHLBI-P01 HL51952"],"award-info":[{"award-number":["NHLBI-P01 HL51952"]}]},{"name":"Unifi Greensboro, NC, USA"},{"name":"Farley Hudson Foundation, Jacksonville, NC, USA"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Endocrinology and Metabolism"],"published-print":{"date-parts":[[2015,11,1]]},"abstract":"<jats:p>The pregnant female human angiotensinogen (hAGN) transgenic rat mated with the male human renin (hREN) transgenic rat is a model of preeclampsia (TgA) with increased blood pressure, proteinuria, and placenta alterations of edema and necrosis at late gestation. We studied vascular responses and the role of COX-derived prostanoids in the uterine artery (UA) at early gestation in this model. TgA UA showed lower stretch response, similar smooth muscle \u03b1-actin content, and lower collagen content compared with Sprague-Dawley (SD) UA. Vasodilation to acetylcholine was similar in SD and TgA UA (64 \u00b1 8 vs. 75 \u00b1 6% of relaxation, P &gt; 0.05), with an acetylcholine-induced contraction in TgA UA that was abolished by preincubation with indomethacin (78 \u00b1 6 vs. 83 \u00b1 11%, P &gt; 0.05). No differences in the contraction to phenylephrine were observed (159 \u00b1 11 vs. 134 \u00b1 12 %K<jats:sub>MAX<\/jats:sub>, P &gt; 0.05), although in TgA UA this response was greatly affected by preincubation with indomethacin (179 \u00b1 16 vs. 134 \u00b1 9 %K<jats:sub>MAX<\/jats:sub>, P &lt; 0.05, pD<jats:sub>2<\/jats:sub>5.92 \u00b1 0.08 vs. 5.85 \u00b1 0.03, P &lt; 0.05). Endothelium-independent vasodilation was lower in TgA UA (92 \u00b1 2 vs. 74 \u00b1 5% preconstricted tone, P &lt; 0.05), and preincubation with indomethacin restored the response to normal values (90 \u00b1 3 vs. 84 \u00b1 3%). Immunostaining showed similar signals for \u03b1-actin, COX-2, and eNOS between groups ( P &gt; 0.05). Plasma thromboxane levels were similar between groups. In summary, TgA UA displays functional alterations at early gestation before the preeclamptic phenotype is established. Inhibition of COX enzymes normalizes some of the functional defects in the TgA UA. An increased role for COX-derived prostanoids in this model of preeclampsia may contribute to the development of a hypertensive pregnancy.<\/jats:p>","DOI":"10.1152\/ajpendo.00526.2014","type":"journal-article","created":{"date-parts":[[2015,9,23]],"date-time":"2015-09-23T03:45:14Z","timestamp":1442979914000},"page":"E811-E817","source":"Crossref","is-referenced-by-count":16,"title":["Functional changes in the uterine artery precede the hypertensive phenotype in a transgenic model of hypertensive pregnancy"],"prefix":"10.1152","volume":"309","author":[{"given":"Victor M.","family":"Pulgar","sequence":"first","affiliation":[{"name":"Hypertension and Vascular Research Center and"},{"name":"Department of Obstetrics and Gynecology, Wake Forest School of Medicine, Winston-Salem, North Carolina;"},{"name":"Biomedical Research and Infrastructure Center, Winston-Salem State University, Winston-Salem, North Carolina;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liliya M.","family":"Yamaleyeva","sequence":"additional","affiliation":[{"name":"Hypertension and Vascular Research Center and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jasmina","family":"Varagic","sequence":"additional","affiliation":[{"name":"Hypertension and Vascular Research Center and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carolynne","family":"McGee","sequence":"additional","affiliation":[{"name":"Hypertension and Vascular Research Center and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Bader","sequence":"additional","affiliation":[{"name":"Max Delbr\u00fcck Center for Molecular Medicine, Berlin-Buch, Germany;"},{"name":"Experimental and Clinical Research Center, Charit\u00e9 University Hospital Berlin, and HELIOS-Clinic, Berlin, Germany; and"},{"name":"Federal University of Minas Gerais, Belo Horizonte, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ralf","family":"Dechend","sequence":"additional","affiliation":[{"name":"Experimental and Clinical Research Center, Charit\u00e9 University Hospital Berlin, and HELIOS-Clinic, Berlin, Germany; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K. 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