{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T10:50:29Z","timestamp":1774263029923,"version":"3.50.1"},"reference-count":55,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2012,7,19]],"date-time":"2012-07-19T00:00:00Z","timestamp":1342656000000},"content-version":"vor","delay-in-days":6896,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[1993,9]]},"abstract":"<jats:p><jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>This study investigates the role of tumour necrosis factor (TNF) in the induction of nitric oxide synthase (NOS) by bacterial endotoxin (lipopolysaccharide; LPS) in a rat model of endotoxin shock.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In anaesthetized rats, pretreatment with a monoclonal antibody for TNF (TNF<jats:sub>ab<\/jats:sub>; 20 mg kg<jats:sup>\u22121<\/jats:sup>, s.c., at 16 h prior to LPS) ameliorated the fall in mean arterial blood pressure (MAP) in response to LPS (2 mg kg<jats:sup>\u22121<\/jats:sup>, i.v.). For instance, endotoxaemia for 180 min resulted in a fall in MAP from 114 \u00b1 6 (control) to 84 \u00b1 5 mmHg (<jats:italic>P<\/jats:italic> &lt; 0.01; <jats:italic>n<\/jats:italic> = 7). In contrast, animals pretreated with TNF<jats:sub>ab<\/jats:sub> prior to LPS injection maintained significantly higher MAP when compared to LPS\u2010control (MAP at 180 min; 118 \u00b1 3 mmHg; <jats:italic>P<\/jats:italic> &lt; 0.01, <jats:italic>n<\/jats:italic> = 5).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Three hours of endotoxaemia was also associated with a significant reduction of the contractile effects of noradrenaline (NA) (10<jats:sup>\u22121<\/jats:sup>\u201310<jats:sup>\u22126<\/jats:sup> <jats:sc>m<\/jats:sc>) on the thoracic aorta <jats:italic>ex vivo<\/jats:italic>. This hyporeactivity to NA was partially restored by <jats:italic>in vitro<\/jats:italic> treatment of the vessels with N<jats:sup>G<\/jats:sup>\u2010nitro\u2010<jats:sc>l<\/jats:sc>\u2010arginine methyl ester (<jats:sc>l<\/jats:sc>\u2010NAME, 20 min, 3 \u00d7 10<jats:sup>\u22124<\/jats:sup> <jats:sc>m<\/jats:sc>). Pretreatment of rats with TNF<jats:sub>ab<\/jats:sub> (20 mg kg<jats:sup>\u22121<\/jats:sup>; at 16 h prior to LPS) significantly (<jats:italic>P<\/jats:italic> &lt; 0.05) attenuated the LPS\u2010induced hyporeactivity of rat aortic rings <jats:italic>ex vivo<\/jats:italic>. <jats:sc>l<\/jats:sc>\u2010NAME did not enhance the contractions of aortic rings obtained from TNF<jats:sub>ab<\/jats:sub> pretreated LPS\u2010rats.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>At 180 min after LPS there was a significant elevation of the induced NOS activity in the lung (5.14 \u00b1 0.57 pmol citrulline mg<jats:sup>\u22121<\/jats:sup> min<jats:sup>\u22121<\/jats:sup>, <jats:italic>n<\/jats:italic> = 8). TNF<jats:sub>ab<\/jats:sub> pretreatment significantly attenuated this induction of NOS in response to LPS by 37 \u00b1 6% (<jats:italic>n<\/jats:italic> = 5; <jats:italic>P<\/jats:italic> &lt; 0.05).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>We conclude that the formation of endogenous TNF contributes to the induction of the calcium\u2010independent isoform of NOS in response to LPS <jats:italic>in vivo<\/jats:italic>. Thus, the beneficial effects of agents which inhibit either the release or the action of TNF in circulatory shock may be, in part, due to inhibition of NOS induction.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p>","DOI":"10.1111\/j.1476-5381.1993.tb13789.x","type":"journal-article","created":{"date-parts":[[2012,7,20]],"date-time":"2012-07-20T00:02:46Z","timestamp":1342742566000},"page":"177-182","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":145,"title":["Role of tumour necrosis factor in the induction of nitric oxide synthase in a rat model of endotoxin shock"],"prefix":"10.1111","volume":"110","author":[{"given":"Christoph","family":"Thiemermann","sequence":"first","affiliation":[]},{"given":"Chin\u2010Chen","family":"Wu","sequence":"additional","affiliation":[]},{"given":"Csaba","family":"Szab\u00f3","sequence":"additional","affiliation":[]},{"given":"Mauro","family":"Perretti","sequence":"additional","affiliation":[]},{"given":"John R.","family":"Vane","sequence":"additional","affiliation":[]}],"member":"311","published-online":{"date-parts":[[2012,7,19]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"crossref","first-page":"3972","DOI":"10.4049\/jimmunol.135.6.3972","article-title":"Cachectin\/tumor necrosis factor: production, distribution and metabolic fate in vivo","volume":"135","author":"BEUTLER B.A.","year":"1985","journal-title":"J. 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