The calcineurin inhibitor cyclosporine A improves lipopolysaccharide- induced vascular dysfunction but does not rescue from cardiovascular collapse in endotoxemic mice

Pflugers Archiv European Journal of Physiology

Volumn 465, Issue 10, 2013, Pages 1467-1475

  Stæhr, Mette ^a   Khatam Lashgari, Apameh ^a   Vanhoutte, Paul M ^b,c   Hansen, Pernille B L ^a   Jensen, Boye L ^a  

^a UNIVERSITY OF SOUTHERN DENMARK   (Denmark)

^b UNIVERSITY OF HONG KONG   (Hong Kong)

^c KING SAUD UNIVERSITY   (Saudi Arabia)

Author keywords

Adrenoceptor; Bradycardia; Endothelium; Hypotension; Sepsis

Indexed keywords

BETA 1 ADRENERGIC RECEPTOR; CYCLOSPORIN A; ENDOTHELIAL NITRIC OXIDE SYNTHASE; INDUCIBLE NITRIC OXIDE SYNTHASE; MESSENGER RNA; NITRIC OXIDE; PHENYLEPHRINE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BLOOD VESSEL REACTIVITY; CONTINUOUS INFUSION; CONTROLLED STUDY; DOSE RESPONSE; ENDOTOXEMIA; FEMALE; HEART RATE; IN VITRO STUDY; IN VIVO STUDY; MALE; MEAN ARTERIAL PRESSURE; MOUSE; NONHUMAN; PRIORITY JOURNAL; SEPTIC SHOCK; TISSUE LEVEL; VASCULAR DISEASE; VASCULAR RESISTANCE; VASCULAR RING;

ANIMALS; AORTA; BLOOD PRESSURE; BRADYCARDIA; CALCINEURIN; CYCLOSPORINE; ENDOTOXEMIA; HEART RATE; HYPOTENSION; INJECTIONS, INTRAVENOUS; LIPOPOLYSACCHARIDES; MICE; MICE, INBRED C57BL; NITRIC OXIDE; NITRIC OXIDE SYNTHASE TYPE II; PHENYLEPHRINE; VASOCONSTRICTION;

EID: 84884888204     PISSN: 00316768     EISSN: 14322013     Source Type: Journal    
DOI: 10.1007/s00424-013-1290-4     Document Type: Article

References (33)

1. 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 29:1303-1310
2. 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 26:660-667
3. 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 24:113-122
4. 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 34:307-313
5. 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 24:1315-1322
6. 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 25:761-767
7. Cauwels A, Janssen B, Buys E, Sips P, Brouckaert P (2006) Anaphylactic shock depends on PI3K and eNOS-derived NO. J Clin Invest 116:2244-2251
8. 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 280:10040-10046
9. 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 128:337-344
10. 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 110:402-409
11. 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 89:3686-3690
12. Hahn PY, Wang P, Tait SM, Ba ZF, Reich SS, Chaudry IH (1995) Sustained elevation in circulating catecholamine levels during polymicrobial sepsis. Shock 4:269-273
13. 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:E871-875
14. Hamalainen M, Korhonen R, Moilanen E (2009) Calcineurin inhibitors down-regulate iNOS expression by destabilizing mRNA. Int Immunopharmacol 9:159-167
15. 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 448:239-244
16. 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 165:7-11
17. 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 15:109-120
18. 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 92:10688-10692
19. 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 14:2634-2638
20. 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 31:3896-3901
21. 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 49:569-576
22. 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 32:21-30
23. 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 81:641-650
24. 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 48:720-723
25. Obias VJ, Rushing GD, Prewitt RL, Rice D, Britt LD (2006) Cyclosporine inhibits endotoxin-induced vasodilation of isolated rat resistance arterioles. J Surg Res 136:112-115
26. 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 259:905-915
27. 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 254:799-808
28. Rusnak F, Mertz P (2000) Calcineurin: form and function. Physiol Rev 80:1483-1521
29. 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:R412-420
30. 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 28:1631-1639
31. Tang C, Liu MS (1996) Initial externalization followed by internalization of beta-adrenergic receptors in rat heart during sepsis. Am J Physiol 270:R254-263
32. 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 375:408-411
33. Winslow MM, Gallo EM, Neilson JR, Crabtree GR (2006) The calcineurin phosphatase complex modulates immunogenic B cell responses. Immunity 24:141-152