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SHR Neuro Krebs Kardio Lipid

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
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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
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