{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T02:19:39Z","timestamp":1774664379507,"version":"3.50.1"},"reference-count":34,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2009,2,10]],"date-time":"2009-02-10T00:00:00Z","timestamp":1234224000000},"content-version":"vor","delay-in-days":4089,"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":[[1997,12]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>In this investigation the NO production rate is quantified in the pig during normotensive endotoxin\u2010induced shock with increased cardiac output and during subsequent treatment with the NO synthase inhibitor N<jats:sup>\u03c9<\/jats:sup>\u2010monomethy\u2010<jats:sc>l<\/jats:sc>\u2010arginine (<jats:sc>l<\/jats:sc>\u2010NMMA). NO production rate was derived from the plasma isotope\u2010enrichment of <jats:sup>15<\/jats:sup>N\u2010labelled nitrate (<jats:sup>15<\/jats:sup>NO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup>).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Three groups of animals (control, <jats:italic>n<\/jats:italic>=5; endotoxin, <jats:italic>n<\/jats:italic>=6; endotoxin+<jats:sc>l<\/jats:sc>\u2010NMMA, <jats:italic>n<\/jats:italic>=6) were anaesthetized and instrumented for the measurement of systemic and pulmonary haemodynamics. Each animal received a primed\u2010continuous infusion of stable, non\u2010radioactively labelled Na<jats:sup>15<\/jats:sup>NO<jats:sub>3<\/jats:sub> (bolus 30\u2003mg, infusion rate 2.1\u2003mg\u2003h<jats:sup>\u22121<\/jats:sup>). Arterial blood samples were taken 5, 10, 15, 30, 60 and 90\u2003min later and every 90 minutes until the end of the experiment.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Continuous i.v. infusion of endotoxin was incrementally adjusted until mean pulmonary artery pressure (PAP) reached 50\u2003mmHg and subsequently titrated to keep mean PAP \u223camp;35\u2003mmHg. Hydroxyethylstarch was administered as required to maintain mean arterial pressure (MAP)&gt;60\u2003mmHg. Six hours after the start of the endotoxin continuous i.v. <jats:sc>l<\/jats:sc>\u2010NMMA (1\u2003mg\u2003kg<jats:sup>\u22121<\/jats:sup>\u2003h<jats:sup>\u22121<\/jats:sup>) was administered to the endotoxin+<jats:sc>l<\/jats:sc>\u2010NMMA group. Haemodynamic data were measured before as well as 9\u2003h after the start of the endotoxin.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>After conversion of NO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup> to nitro\u2010trimethoxybenzene and gas chromatography\u2010mass spectrometry analysis the total NO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup> pool, basal NO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup> production rate and the increase per unit time in NO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup> production rate were calculated from the time\u2010course of the <jats:sup>15<\/jats:sup>NO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup> plasma isotope\u2010enrichment. A two compartment model was assumed for the NO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup> kinetics, one being an active pool in which newly generated NO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup> appears and from which it is eliminated, the other being an inactive volume of distribution in which only passive exchange takes place with the active compartment.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Although MAP did not change during endotoxin infusion alone, cardiac output (CO) increased by 42\u00b140% (<jats:italic>P<\/jats:italic>&lt;0.05 versus baseline) by the end of the experiment due to a significant (<jats:italic>P<\/jats:italic>&lt;0.05 versus baseline) fall in systemic vascular resistance (SVR) to 65\u00b125% of the baseline value. <jats:sc>l<\/jats:sc>\u2010NMMA given with endotoxin did not change MAP, and both CO and SVR were maintained close to the pre\u2010shock levels.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Baseline plasma NO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup> concentrations were 43\u00b113 and 40\u00b110\u2003\u03bcmol\u2003l<jats:sup>\u22121<\/jats:sup> in the control and endotoxin animals, respectively, and did not differ at the end of the experiment (39\u00b18 and 44\u00b115\u2003\u03bcmol\u2003l<jats:sup>\u22121<\/jats:sup>, respectively). The mean NO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup> pool and basal NO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup> production rate were 1155\u00b1294\u2003\u03bcmol and 140\u00b132\u2003\u03bcmol\u2003h<jats:sup>\u22121<\/jats:sup>, respectively, without any intergroup difference. Endotoxin significantly increased NO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup> production rate (23\u00b110\u2003\u03bcmol\u2003h<jats:sup>\u22122<\/jats:sup>, <jats:italic>P<\/jats:italic>&lt;0.05 versus control (6\u00b17\u2003\u03bcmol\u2003h<jats:sup>\u22122<\/jats:sup>) and endotoxin+<jats:sc>l<\/jats:sc>\u2010NMMA groups). <jats:sc>l<\/jats:sc>\u2010NMMA given with endotoxin (\u22121\u00b12\u2003\u03bcmol\u2003h<jats:sup>\u22122<\/jats:sup>, <jats:italic>P<\/jats:italic>&lt;0.05 versus control and endotoxin groups) had no effect.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Analysis of the time course of the <jats:sup>15<\/jats:sup>NO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup> plasma isotope enrichment during primed\u2010continuous infusion of Na<jats:sup>15<\/jats:sup>NO<jats:sub>3<\/jats:sub> allowed us to quantify the endotoxin\u2010induced increase in NO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup> production rate independently of total NO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup> plasma concentrations. Low\u2010dose <jats:sc>l<\/jats:sc>\u2010NMMA blunted the increase in NO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup> production rate while maintaining basal NO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup> formation.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p>","DOI":"10.1038\/sj.bjp.0701553","type":"journal-article","created":{"date-parts":[[2005,1,28]],"date-time":"2005-01-28T19:18:29Z","timestamp":1106939909000},"page":"1605-1610","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["<i>In vivo<\/i> quantification of endotoxin\u2010induced nitric oxide production in pigs from Na<sup>15<\/sup>NO<sub>3<\/sub>\u2010infusion"],"prefix":"10.1111","volume":"122","author":[{"given":"Borislav","family":"\u0160antak","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Radermacher","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Iber","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jens","family":"Adler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ulrich","family":"Wachter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Damian","family":"Vassilev","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Georgieff","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Josef","family":"Vogt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,2,10]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.7.2.8440411"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/00024382-199605000-00009"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.21.11460"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.1995.268.2.E360"},{"key":"e_1_2_6_6_1","first-page":"416","article-title":"Effect of Hr antagonism on cardiovascular, pulmonary, and immunologic dysfunction in porcine endotoxic shock","volume":"3","author":"DIMMEIER S.","year":"1995","journal-title":"Shock"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1439-0396.1982.tb01391.x"},{"key":"e_1_2_6_8_1","first-page":"77","article-title":"Evidence of increased nitric oxide production in patients with the sepsis syndrome","volume":"41","author":"EVANS T.","year":"1993","journal-title":"Circ. 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