Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Bosche, B; Molcanyi, M; Noll, T; Rej, S; Zatschler, B; Doeppner, TR; Hescheler, J; Müller, DJ; Macdonald, RL; Härtel, FV.
A differential impact of lithium on endothelium-dependent but not on endothelium-independent vessel relaxation.
Prog Neuropsychopharmacol Biol Psychiatry. 2016; 67(4):98-106
Doi: 10.1016/j.pnpbp.2016.02.004
Web of Science
PubMed
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FullText_MUG
- Co-Autor*innen der Med Uni Graz
- Molcanyi Marek
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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. We hypothesize 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. Copyright © 2016 Elsevier Inc. All rights reserved.
- Find related publications in this database (using NLM MeSH Indexing)
- Acetylcholine - pharmacology
- Animals -
- Antimanic Agents - pharmacology
- Dose-Response Relationship, Drug -
- Endothelium, Vascular - drug effects
- Enzyme Inhibitors - pharmacology
- Isometric Contraction - drug effects
- Lithium Chloride - pharmacology
- Macrocyclic Compounds - pharmacology
- Mice -
- Nitric Oxide Synthase - metabolism
- Oxazoles - pharmacology
- Phenylephrine - pharmacology
- Statistics, Nonparametric -
- Swine -
- Time Factors -
- Vasoconstrictor Agents - pharmacology
- Vasodilation - drug effects
- Vasodilator Agents - pharmacology
- Find related publications in this database (Keywords)
- Lithium
- Adverse effects of lithium
- Bipolar disorder
- Stroke
- Endothelium
- Vascular relaxation
- Vascular autoregulation
- Cerebrovascular autoregulation
- Endothelial function