{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T20:37:09Z","timestamp":1761597429273,"version":"3.40.4"},"reference-count":33,"publisher":"Springer Science and Business Media LLC","issue":"10","license":[{"start":{"date-parts":[[2013,5,21]],"date-time":"2013-05-21T00:00:00Z","timestamp":1369094400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pflugers Arch - Eur J Physiol"],"published-print":{"date-parts":[[2013,10]]},"DOI":"10.1007\/s00424-013-1290-4","type":"journal-article","created":{"date-parts":[[2013,5,20]],"date-time":"2013-05-20T09:17:26Z","timestamp":1369041446000},"page":"1467-1475","source":"Crossref","is-referenced-by-count":10,"title":["The calcineurin inhibitor cyclosporine A improves lipopolysaccharide-induced vascular dysfunction but does not rescue from cardiovascular collapse in endotoxemic mice"],"prefix":"10.1007","volume":"465","author":[{"given":"Mette","family":"St\u00e6hr","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Apameh","family":"Khatam-Lashgari","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul M.","family":"Vanhoutte","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pernille B. L.","family":"Hansen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Boye L.","family":"Jensen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2013,5,21]]},"reference":[{"key":"1290_CR1","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1097\/00003246-200107000-00002","volume":"29","author":"DC Angus","year":"2001","unstructured":"Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR (2001) Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med 29:1303\u20131310","journal-title":"Crit Care Med"},{"key":"1290_CR2","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1097\/00003246-199804000-00012","volume":"26","author":"JA Avontuur","year":"1998","unstructured":"Avontuur JA, Tutein Nolthenius RP, Van Bodegom JW, Bruining HA (1998) Prolonged inhibition of nitric oxide synthesis in severe septic shock: a clinical study. Crit Care Med 26:660\u2013667","journal-title":"Crit Care Med"},{"key":"1290_CR3","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.niox.2011.01.002","volume":"24","author":"JM Balibrea","year":"2011","unstructured":"Balibrea JM, Garcia-Martin MC, Cuesta-Sancho S, Olmedilla Y, Arias-Diaz J, Fernandez-Sevilla E, Vara E, Balibrea JL (2011) Tacrolimus modulates liver and pancreas nitric oxide synthetase and heme-oxygenase isoforms and cytokine production after endotoxemia. Nitric Oxide 24:113\u2013122","journal-title":"Nitric Oxide"},{"key":"1290_CR4","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1097\/01.CCM.0000199070.46812.21","volume":"34","author":"E Barth","year":"2006","unstructured":"Barth E, Radermacher P, Thiemermann C, Weber S, Georgieff M, Albuszies G (2006) Role of inducible nitric oxide synthase in the reduced responsiveness of the myocardium to catecholamines in a hyperdynamic, murine model of septic shock. Crit Care Med 34:307\u2013313","journal-title":"Crit Care Med"},{"key":"1290_CR5","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.1007\/s001340050768","volume":"24","author":"G Bernardin","year":"1998","unstructured":"Bernardin G, Strosberg AD, Bernard A, Mattei M, Marullo S (1998) Beta-adrenergic receptor-dependent and -independent stimulation of adenylate cyclase is impaired during severe sepsis in humans. Intensive Care Med 24:1315\u20131322","journal-title":"Intensive Care Med"},{"key":"1290_CR6","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1016\/0735-1097(94)00425-P","volume":"25","author":"OE Brodde","year":"1995","unstructured":"Brodde OE, Adamczyk M, Busch F, Bossaller C, Duske E, Fleck E, Gotze S, Auch-Schwelk W (1995) Selective downregulation of rat cardiac beta 1-adrenoceptors by cyclosporine A: prevention by diltiazem or angiotensin-converting enzyme inhibitors. J Am Coll Cardiol 25:761\u2013767","journal-title":"J Am Coll Cardiol"},{"key":"1290_CR7","doi-asserted-by":"crossref","first-page":"2244","DOI":"10.1172\/JCI25426","volume":"116","author":"A Cauwels","year":"2006","unstructured":"Cauwels A, Janssen B, Buys E, Sips P, Brouckaert P (2006) Anaphylactic shock depends on PI3K and eNOS-derived NO. J Clin Invest 116:2244\u20132251","journal-title":"J Clin Invest"},{"key":"1290_CR8","doi-asserted-by":"crossref","first-page":"10040","DOI":"10.1074\/jbc.M411991200","volume":"280","author":"L Connelly","year":"2005","unstructured":"Connelly L, Madhani M, Hobbs AJ (2005) Resistance to endotoxic shock in endothelial nitric-oxide synthase (eNOS) knock-out mice: a pro-inflammatory role for eNOS-derived no in vivo. J Biol Chem 280:10040\u201310046","journal-title":"J Biol Chem"},{"key":"1290_CR9","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1038\/sj.bjp.0702782","volume":"128","author":"GJ Dusting","year":"1999","unstructured":"Dusting GJ, Akita K, Hickey H, Smith M, Gurevich V (1999) Cyclosporin A and tacrolimus (FK506) suppress expression of inducible nitric oxide synthase in vitro by different mechanisms. Br J Pharmacol 128:337\u2013344","journal-title":"Br J Pharmacol"},{"key":"1290_CR10","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1016\/0002-8703(85)90163-2","volume":"110","author":"AG Ellrodt","year":"1985","unstructured":"Ellrodt AG, Riedinger MS, Kimchi A, Berman DS, Maddahi J, Swan HJ, Murata GH (1985) Left ventricular performance in septic shock: reversible segmental and global abnormalities. Am Hear J 110:402\u2013409","journal-title":"Am Hear J"},{"key":"1290_CR11","doi-asserted-by":"crossref","first-page":"3686","DOI":"10.1073\/pnas.89.9.3686","volume":"89","author":"DA Fruman","year":"1992","unstructured":"Fruman DA, Klee CB, Bierer BE, Burakoff SJ (1992) Calcineurin phosphatase activity in T lymphocytes is inhibited by FK 506 and cyclosporin A. Proc Natl Acad Sci U S A 89:3686\u20133690","journal-title":"Proc Natl Acad Sci U S A"},{"key":"1290_CR12","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1097\/00024382-199510000-00007","volume":"4","author":"PY Hahn","year":"1995","unstructured":"Hahn PY, Wang P, Tait SM, Ba ZF, Reich SS, Chaudry IH (1995) Sustained elevation in circulating catecholamine levels during polymicrobial sepsis. Shock 4:269\u2013273","journal-title":"Shock"},{"key":"1290_CR13","first-page":"E871","volume":"285","author":"MM Hallemeesch","year":"2003","unstructured":"Hallemeesch MM, Janssen BJ, De Jonge WJ, Soeters PB, Lamers WH, Deutz NE (2003) NO production by cNOS and iNOS reflects blood pressure changes in LPS-challenged mice. Am J Physiol 285:E871\u2013875","journal-title":"Am J Physiol"},{"key":"1290_CR14","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.intimp.2008.07.012","volume":"9","author":"M Hamalainen","year":"2009","unstructured":"Hamalainen M, Korhonen R, Moilanen E (2009) Calcineurin inhibitors down-regulate iNOS expression by destabilizing mRNA. Int Immunopharmacol 9:159\u2013167","journal-title":"Int Immunopharmacol"},{"key":"1290_CR15","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/S0014-2999(02)01947-7","volume":"448","author":"M Hamalainen","year":"2002","unstructured":"Hamalainen M, Lahti A, Moilanen E (2002) Calcineurin inhibitors, cyclosporin A and tacrolimus inhibit expression of inducible nitric oxide synthase in colon epithelial and macrophage cell lines. Eur J Pharmacol 448:239\u2013244","journal-title":"Eur J Pharmacol"},{"key":"1290_CR16","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1006\/cimm.1995.1180","volume":"165","author":"Y Hattori","year":"1995","unstructured":"Hattori Y, Nakanishi N (1995) Effects of cyclosporin A and FK506 on nitric oxide and tetrahydrobiopterin synthesis in bacterial lipopolysaccharide-treated J774 macrophages. Cell Immunol 165:7\u201311","journal-title":"Cell Immunol"},{"key":"1290_CR17","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1177\/1753425908100928","volume":"15","author":"C Jennings","year":"2009","unstructured":"Jennings C, Kusler B, Jones PP (2009) Calcineurin inactivation leads to decreased responsiveness to LPS in macrophages and dendritic cells and protects against LPS-induced toxicity in vivo. Innate Immun 15:109\u2013120","journal-title":"Innate Immun"},{"key":"1290_CR18","doi-asserted-by":"crossref","first-page":"10688","DOI":"10.1073\/pnas.92.23.10688","volume":"92","author":"VE Laubach","year":"1995","unstructured":"Laubach VE, Shesely EG, Smithies O, Sherman PA (1995) Mice lacking inducible nitric oxide synthase are not resistant to lipopolysaccharide-induced death. Proc Natl Acad Sci U S A 92:10688\u201310692","journal-title":"Proc Natl Acad Sci U S A"},{"key":"1290_CR19","doi-asserted-by":"crossref","first-page":"2634","DOI":"10.1093\/ndt\/14.11.2634","volume":"14","author":"J Lee","year":"1999","unstructured":"Lee J, Kim SW, Kook H, Kang DG, Kim NH, Choi KC (1999) Effects of L-arginine on cyclosporin-induced alterations of vascular NO\/cGMP generation. Nephrol Dial Transplant 14:2634\u20132638","journal-title":"Nephrol Dial Transplant"},{"key":"1290_CR20","doi-asserted-by":"crossref","first-page":"3896","DOI":"10.1021\/bi00131a002","volume":"31","author":"J Liu","year":"1992","unstructured":"Liu J, Albers MW, Wandless TJ, Luan S, Alberg DG, Belshaw PJ, Cohen P, Mackintosh C, Klee CB, Schreiber SL (1992) Inhibition of T cell signaling by immunophilin-ligand complexes correlates with loss of calcineurin phosphatase activity. Biochemistry 31:3896\u20133901","journal-title":"Biochemistry"},{"key":"1290_CR21","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1161\/01.HYP.0000257914.80918.72","volume":"49","author":"C Long","year":"2007","unstructured":"Long C, Cook LG, Hamilton SL, Wu GY, Mitchell BM (2007) FK506 binding protein 12\/12.6 depletion increases endothelial nitric oxide synthase threonine 495 phosphorylation and blood pressure. Hypertension 49:569\u2013576","journal-title":"Hypertension"},{"key":"1290_CR22","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1097\/01.CCM.0000105581.01815.C6","volume":"32","author":"A Lopez","year":"2004","unstructured":"Lopez A, Lorente JA, Steingrub J, Bakker J, Mcluckie A, Willatts S, Brockway M, Anzueto A, Holzapfel L, Breen D, Silverman MS, Takala J, Donaldson J, Arneson C, Grove G, Grossman S, Grover R (2004) Multiple-center, randomized, placebo-controlled, double-blind study of the nitric oxide synthase inhibitor 546C88: effect on survival in patients with septic shock. Crit Care Med 32:21\u201330","journal-title":"Crit Care Med"},{"key":"1290_CR23","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1016\/0092-8674(95)90085-3","volume":"81","author":"JD Macmicking","year":"1995","unstructured":"Macmicking JD, Nathan C, Hom G, Chartrain N, Fletcher DS, Trumbauer M, Stevens K, Xie QW, Sokol K, Hutchinson N (1995) Altered responses to bacterial infection and endotoxic shock in mice lacking inducible nitric oxide synthase. Cell 81:641\u2013650","journal-title":"Cell"},{"key":"1290_CR24","first-page":"720","volume":"48","author":"PL Mottram","year":"1989","unstructured":"Mottram PL, Mirisklavas A, Mason A, Dumble LJ, Smith JA, Clunie GJ, Panagiotopoulos S, Nayler WG (1989) Immunosuppressive and cardiotoxic effects of cyclosporine in CBA mice. Transplantation 48:720\u2013723","journal-title":"Transplantation"},{"key":"1290_CR25","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.jss.2006.04.026","volume":"136","author":"VJ Obias","year":"2006","unstructured":"Obias VJ, Rushing GD, Prewitt RL, Rice D, Britt LD (2006) Cyclosporine inhibits endotoxin-induced vasodilation of isolated rat resistance arterioles. J Surg Res 136:112\u2013115","journal-title":"J Surg Res"},{"key":"1290_CR26","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1016\/S0022-3565(25)20565-1","volume":"259","author":"A Rego","year":"1991","unstructured":"Rego A, Vargas R, Cathapermal S, Kuwahara M, Foegh ML, Ramwell PW (1991) Systemic vascular effects of cyclosporin A treatment in normotensive rats. J Pharmacol Exp Ther 259:905\u2013915","journal-title":"J Pharmacol Exp Ther"},{"key":"1290_CR27","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1016\/S0022-3565(25)12732-8","volume":"254","author":"A Rego","year":"1990","unstructured":"Rego A, Vargas R, Suarez KR, Foegh ML, Ramwell PW (1990) Mechanism of cyclosporin potentiation of vasoconstriction of the isolated rat mesenteric arterial bed: role of extracellular calcium. J Pharmacol Exp Ther 254:799\u2013808","journal-title":"J Pharmacol Exp Ther"},{"key":"1290_CR28","doi-asserted-by":"crossref","first-page":"1483","DOI":"10.1152\/physrev.2000.80.4.1483","volume":"80","author":"F Rusnak","year":"2000","unstructured":"Rusnak F, Mertz P (2000) Calcineurin: form and function. Physiol Rev 80:1483\u20131521","journal-title":"Physiol Rev"},{"key":"1290_CR29","doi-asserted-by":"crossref","first-page":"R412","DOI":"10.1152\/ajpregu.00823.2010","volume":"301","author":"M Staehr","year":"2011","unstructured":"Staehr M, Madsen K, Vanhoutte PM, Hansen PB, Jensen BL (2011) Disruption of COX-2 and eNOS does not confer protection from cardiovascular failure in lipopolysaccharide-treated conscious mice and isolated vascular rings. Am J Physiol Regul Integr Comp Physiol 301:R412\u2013420","journal-title":"Am J Physiol Regul Integr Comp Physiol"},{"key":"1290_CR30","doi-asserted-by":"crossref","first-page":"1631","DOI":"10.1006\/jmcc.1996.0153","volume":"28","author":"B Stein","year":"1996","unstructured":"Stein B, Frank P, Schmitz W, Scholz H, Thoenes M (1996) Endotoxin and cytokines induce direct cardiodepressive effects in mammalian cardiomyocytes via induction of nitric oxide synthase. J Mol Cell Cardiol 28:1631\u20131639","journal-title":"J Mol Cell Cardiol"},{"key":"1290_CR31","first-page":"R254","volume":"270","author":"C Tang","year":"1996","unstructured":"Tang C, Liu MS (1996) Initial externalization followed by internalization of beta-adrenergic receptors in rat heart during sepsis. Am J Physiol 270:R254\u2013263","journal-title":"Am J Physiol"},{"key":"1290_CR32","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1038\/375408a0","volume":"375","author":"XQ Wei","year":"1995","unstructured":"Wei XQ, Charles IG, Smith A, Ure J, Feng GJ, Huang FP, Xu D, Muller W, Moncada S, Liew FY (1995) Altered immune responses in mice lacking inducible nitric oxide synthase. Nature 375:408\u2013411","journal-title":"Nature"},{"key":"1290_CR33","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.immuni.2005.12.013","volume":"24","author":"MM Winslow","year":"2006","unstructured":"Winslow MM, Gallo EM, Neilson JR, Crabtree GR (2006) The calcineurin phosphatase complex modulates immunogenic B cell responses. Immunity 24:141\u2013152","journal-title":"Immunity"}],"container-title":["Pfl\u00fcgers Archiv - European Journal of Physiology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00424-013-1290-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s00424-013-1290-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00424-013-1290-4","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,30]],"date-time":"2025-04-30T10:39:11Z","timestamp":1746009551000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s00424-013-1290-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,5,21]]},"references-count":33,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2013,10]]}},"alternative-id":["1290"],"URL":"https:\/\/doi.org\/10.1007\/s00424-013-1290-4","relation":{},"ISSN":["0031-6768","1432-2013"],"issn-type":[{"type":"print","value":"0031-6768"},{"type":"electronic","value":"1432-2013"}],"subject":[],"published":{"date-parts":[[2013,5,21]]}}}