{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T12:11:13Z","timestamp":1791288673453,"version":"4.3.0"},"reference-count":49,"publisher":"American Physiological Society","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2004,12]]},"abstract":"<jats:p> We reported previously that endothelium-intact superior mesenteric arteries (SMA) from N<jats:sup>\u03c9<\/jats:sup>-nitro-l-arginine (l-NNA)-treated hypertensive rats (LHR) contract more to norepinephrine (NE) than SMA from control rats. Others have shown that nitric oxide (NO) synthase (NOS) inhibition increases cyclooxygenase (COX) function and expression. We hypothesized that augmented vascular sensitivity to NE in LHR arteries is caused by decreased NOS-induced dilation and increased COX product-induced constriction. We observed that the EC<jats:sub>50<\/jats:sub> for NE is lower in LHR SMA compared with control SMA (control \u22126.37 \u00b1 0.04, LHR \u22127.89 \u00b1 0.09 log mol\/l; P &lt; 0.05). Endothelium removal lowered the EC<jats:sub>50<\/jats:sub> (control \u22127.95 \u00b1 0.11, LHR \u22128.44 \u00b1 0.13 log mol\/l; P &lt; 0.05) and increased maximum tension in control (control 1,036 \u00b1 38 vs. 893 \u00b1 21 mg; P &lt; 0.05) but not LHR (928 \u00b1 30 vs. 1,066 \u00b1 31 mg) SMA. Thus augmented NE sensitivity in LHR SMA depends largely on decreased endothelial dilation. NOS inhibition (l-NNA, 10<jats:sup>\u22124<\/jats:sup> mol\/l) increased maximum tension and EC<jats:sub>50<\/jats:sub> in control arteries but not in LHR arteries. In contrast, COX inhibition decreased maximum tension in control arteries, suggesting that COX products augment contraction. Indomethacin did not affect NE-induced contraction in l-NNA-treated or denuded arteries. In control SMA loaded with the fluorescent NO indicator 4-amino-5-methylamino-2\u2032,7\u2032-difluorofluorescein diacetate, indomethacin increased and l-NNA decreased NO release. Therefore, COX products appear to inhibit NO production to augment NE-induced contraction. With chronic NOS inhibition, this modulating influence is greatly diminished. Thus, in NOS-inhibition hypertension, decreased activity of both COX and NOS pathways profoundly disrupts endothelial modulation of contraction. <\/jats:p>","DOI":"10.1152\/ajpheart.00628.2004","type":"journal-article","created":{"date-parts":[[2004,8,20]],"date-time":"2004-08-20T03:10:16Z","timestamp":1092971416000},"page":"H2394-H2401","source":"Crossref","is-referenced-by-count":16,"title":["Nitric oxide synthase-inhibition hypertension is associated with altered endothelial cyclooxygenase function"],"prefix":"10.1152","volume":"287","author":[{"given":"Ian N.","family":"Bratz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy L.","family":"Kanagy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.15.6.699"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1472-8206.1997.tb00193.x"},{"key":"R3","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.30.4.934"},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00824.2001"},{"key":"R5","unstructured":"Brovkovych V, Dobrucki LW, Brovkovych S, Dobrucki I, Do Nascimento CA, Burewicz A, and Malinski T. 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