Bosche, Bert, Molcanyi, Marek, Noll, Thomas, Rej, Soham, Zatschler, Birgit, Doeppner, Thorsten R., Hescheler, Juergen, Mueller, Daniel J., Macdonald, R. Loch and Haertel, Frauke V. (2016). A differential impact of lithium on endothelium-dependent but not on endothelium-independent vessel relaxation. Prog. Neuro-Psychopharmacol. Biol. Psychiatry, 67. S. 98 - 107. OXFORD: PERGAMON-ELSEVIER SCIENCE LTD. ISSN 1878-4216

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Abstract

Lithium is drug for bipolar disorders with a narrow therapeutic window. Lithium was recently reported to prevent stroke and protect vascular endothelium but tends to accumulate particularly in the brain and kidney. Here, adverse effects are common; however mechanisms are still vaguely understood. If lithium could also negatively influence the endothelium is unclear. Wehypothesize that at higher lithium levels, the effects on endothelium reverses - that lithium also impairs endothelial-dependent relaxation of blood vessels. Vessel grafts from de-nerved murine aortas and porcine middle cerebral arteries were preconditioned using media supplemented with lithium chloride or acetate (0.4-100 mmol/L). Native or following phenylephrine-induced vasoconstriction, the relaxation capacity of preconditioned vessels was assessed by isometric myography, using acetylcholine to test the endothelium-dependent or sodium nitroprusside to test the endothelium-independent vasorelaxation, respectively. At the 0.4 mmol/L lithium concentration, acetylcholine-induced endothelium-dependent vessel relaxation was slightly increased, however, diminished in a concentration-dependent manner in vessel grafts preconditioned with lithium at higher therapeutic and supratherapeutic concentrations (0.8-100 mmol/L). In contrast, endothelium-independent vasorelaxation remained unaltered in preconditioned vessel grafts at any lithium concentration tested. Lithium elicits opposing effects on endothelial functions representing a differential impact on the endothelium within the narrow therapeutic window. Lithium accumulation or overdose reduces endothelium-dependent but not endothelium-independent vasorelaxation. The differentially modified endothelium-dependent vascular response represents an additional mechanism contributing to therapeutic or adverse effects of lithium. (C) 2016 Elsevier Inc. All rights reserved.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Bosche, BertUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Molcanyi, MarekUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Noll, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rej, SohamUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zatschler, BirgitUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Doeppner, Thorsten R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hescheler, JuergenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mueller, Daniel J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Macdonald, R. LochUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Haertel, Frauke V.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-272519
DOI: 10.1016/j.pnpbp.2016.02.004
Journal or Publication Title: Prog. Neuro-Psychopharmacol. Biol. Psychiatry
Volume: 67
Page Range: S. 98 - 107
Date: 2016
Publisher: PERGAMON-ELSEVIER SCIENCE LTD
Place of Publication: OXFORD
ISSN: 1878-4216
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
CHRONIC KIDNEY-DISEASE; BIPOLAR DISORDER; INOSITOL TRISPHOSPHATE; DIABETES-MELLITUS; MOOD DISORDERS; NITRIC-OXIDE; CALCIUM; SYNTHASE; RISK; INTERVENTIONMultiple languages
Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; PsychiatryMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/27251

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