{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T22:36:40Z","timestamp":1770071800702,"version":"3.49.0"},"reference-count":43,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2009,2,3]],"date-time":"2009-02-03T00:00:00Z","timestamp":1233619200000},"content-version":"vor","delay-in-days":3900,"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":[[1998,6]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>The release of cytokines following administration of endotoxin and the contribution of nitric oxide (NO) to the subsequent haemodynamic profile were investigated in the conscious mouse.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Administration of endotoxin (<jats:italic>E. Coli<\/jats:italic>, 026:B6, 12.5 mg kg<jats:sup>\u22121<\/jats:sup>, i.v.) elevated the concentration of tumour necrosis factor\u2010\u03b1 (TNF\u2010\u03b1) in the plasma within 0.5 h, reaching a maximum at 2 h and returning to control concentrations by 4 h. In addition, the concentration of interleukin\u20106 (IL\u20106) in the plasma was also elevated within 1 h, reaching a maximum at 3 h and remaining elevated throughout the 12 h of study.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Endotoxin (12.5 mg kg<jats:sup>\u22121<\/jats:sup>, i.v.) induced the expression of a Ca<jats:sup>2+<\/jats:sup>\u2010independent (inducible) NO synthase in the mouse heart and elevated the concentrations of nitrite and nitrate in the plasma within 4 h, reaching a maximum at 12 h. This was accompanied by a progressive fall in blood pressure over the same period.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The vasopressor effect of noradrenaline (0.5\u20134 \u03bcg kg<jats:sup>\u22121<\/jats:sup> min<jats:sup>\u22121<\/jats:sup>, i.v.) administered as a continuous infusion was significantly attenuated 7 h after endotoxin (12.5 mg kg<jats:sup>\u22121<\/jats:sup>, i.v).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The NO synthase inhibitor N<jats:sup>G<\/jats:sup>\u2010monomethyl\u2010<jats:sc>L<\/jats:sc>\u2010arginine HCl (<jats:sc>L<\/jats:sc>\u2010NMMA; 1\u201310 mg kg<jats:sup>\u22121<\/jats:sup>, i.v. bolus) reversed the fall in blood pressure when administered 7 h after endotoxin (12.5 mg kg<jats:sup>\u22121<\/jats:sup>, i.v.).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In an attempt to maintain a constant blood concentration, <jats:sc>L<\/jats:sc>\u2010NMMA was administered as a continuous infusion (10 mg kg<jats:sup>\u22121<\/jats:sup> h<jats:sup>\u22121<\/jats:sup>, i.v.), beginning 4 h after a lower dose of endotoxin (6 mg kg<jats:sup>\u22121<\/jats:sup>, i.v.). Such treatment prevented the fall in blood pressure and the elevation of nitrite and nitrate in the plasma throughout the 18 h of observation.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The fall in blood pressure following endotoxin (3 mg kg<jats:sup>\u22121<\/jats:sup>, i.v.) was significantly reduced throughout the 18 h of observation in homozygous mutant mice lacking the inducible NO synthase.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In summary, we have developed a model of endotoxin shock in the conscious mouse in which an overproduction of NO by the inducible NO synthase is associated with the haemodynamic disturbances. This model, which exhibits many of the characteristics of septic shock in man, will enable the study of the pathology of this condition in more detail and aid the investigation of potential therapeutic agents both as prophylactics and, more importantly, as treatments.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p>","DOI":"10.1038\/sj.bjp.0701815","type":"journal-article","created":{"date-parts":[[2005,1,28]],"date-time":"2005-01-28T19:30:25Z","timestamp":1106940625000},"page":"540-546","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":68,"title":["Nitric oxide and the haemodynamic profile of endotoxin shock in the conscious mouse"],"prefix":"10.1111","volume":"124","author":[{"given":"D D","family":"Rees","sequence":"first","affiliation":[]},{"given":"J E","family":"Monkhouse","sequence":"additional","affiliation":[]},{"given":"D","family":"Cambridge","sequence":"additional","affiliation":[]},{"given":"S","family":"Moncada","sequence":"additional","affiliation":[]}],"member":"311","published-online":{"date-parts":[[2009,2,3]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"crossref","first-page":"3517","DOI":"10.4049\/jimmunol.143.11.3517","article-title":"IL\u20106 inhibits lipopoly\u2010saccharide\u2010induced tumor necrosis factor production in cultured human monocytes, U937 cells, and in mice","volume":"143","author":"Aderka D.","year":"1989","journal-title":"J. Immunol."},{"key":"e_1_2_6_3_1","first-page":"1","article-title":"Plasma noradrenaline and adrenaline concentrations and dopamine\u2010\u03b2\u2010hydroxylase activity in patients with shock due to septicaemia, trauma and haemorrhage","volume":"185","author":"Benedict C.R.","year":"1978","journal-title":"Q. J. Med."},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0272-5231(05)70307-5"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(95)11703-Y"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000658-199204000-00009"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1006\/cyto.1995.0056"},{"key":"e_1_2_6_8_1","first-page":"77","article-title":"Evidence of increased nitric oxide production in patients with sepsis syndrome","volume":"41","author":"Evans T.","year":"1993","journal-title":"Circ. Shock"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01709327"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1995.tb16405.x"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/00004872-199312000-00009"},{"key":"e_1_2_6_12_1","first-page":"59","article-title":"Dose\u2010 and time\u2010dependent changes in plasma catecholamines in response to endotoxin in conscious rats","volume":"28","author":"Jones S.B.","year":"1989","journal-title":"Circ. Shock"},{"key":"e_1_2_6_13_1","first-page":"H1038","article-title":"Loss of vascular responsiveness induced by endotoxin involves L\u2010arginine pathway","volume":"259","author":"Julou\u2010Schaeffer G.","year":"1990","journal-title":"Am. J. Physiol."},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(95)00281-O"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90085-3"},{"key":"e_1_2_6_16_1","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1152\/jappl.1992.73.1.324","article-title":"Reversal of hyperdynamic response to continuous endotoxin administration by inhibition of NO synthesis","volume":"73","author":"Meyer J.","year":"1992","journal-title":"J. Appl. Physiol."},{"key":"e_1_2_6_17_1","first-page":"109","article-title":"Nitric oxide: physiology, pathophysiology, and pharmacology","volume":"43","author":"Moncada S.","year":"1991","journal-title":"Pharmacol. Rev."},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005344-199204002-00037"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000658-199111000-00013"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199305203282008"},{"key":"e_1_2_6_21_1","first-page":"191","article-title":"Preparation and characterization of NG\u2010mono\u2010,di\u2010 and trimethylated arginines","volume":"12","author":"Patthy A.","year":"1977","journal-title":"Acta Biochim. Biophys. Acad. Sci. Hung."},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(91)92376-D"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/28.1.34"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.3109\/07853899509002585"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1042\/bst0231025"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(05)80068-3"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1995.tb17193.x"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.86.9.3375"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1990.tb14151.x"},{"key":"e_1_2_6_30_1","first-page":"502","volume-title":"Harrison's Principles of Internal Medicine","author":"Root R.K.","year":"1991"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199302113280605"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(91)81123-P"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.7164\/antibiotics.25.179"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1097\/00024382-199407000-00002"},{"key":"e_1_2_6_35_1","doi-asserted-by":"crossref","first-page":"3884","DOI":"10.4049\/jimmunol.142.11.3884","article-title":"Generation and characterization of hamster monoclonal antibodies that neutralize murine tumour necrosis factors","volume":"142","author":"Sheehan K.C.F.","year":"1989","journal-title":"J. Immunol."},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/162.2.421"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198908033210503"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199305203282005"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1054-3589(08)60493-7"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(90)90062-B"},{"key":"e_1_2_6_41_1","first-page":"77","article-title":"Role of endogenous nitric oxide in septic shock","volume":"1","author":"Vallance P.","year":"1993","journal-title":"New Horiz."},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02388298"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/26.1.48"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/375408a0"}],"container-title":["British Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1038%2Fsj.bjp.0701815","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1038%2Fsj.bjp.0701815","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1038\/sj.bjp.0701815","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,28]],"date-time":"2023-10-28T02:16:47Z","timestamp":1698459407000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1038\/sj.bjp.0701815"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1998,6]]},"references-count":43,"journal-issue":{"issue":"3","published-print":{"date-parts":[[1998,6]]}},"alternative-id":["10.1038\/sj.bjp.0701815"],"URL":"https:\/\/doi.org\/10.1038\/sj.bjp.0701815","archive":["Portico"],"relation":{},"ISSN":["0007-1188","1476-5381"],"issn-type":[{"value":"0007-1188","type":"print"},{"value":"1476-5381","type":"electronic"}],"subject":[],"published":{"date-parts":[[1998,6]]},"assertion":[{"value":"2009-02-03","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}