A differential impact of lithium on endothelium-dependent but not on endothelium-independent vessel relaxation

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Bert Bosche - , University of Toronto, University of Duisburg-Essen (Author)
  • Marek Molcanyi - , University of Cologne (Author)
  • Thomas Noll - , TUD Dresden University of Technology (Author)
  • Soham Rej - , University of Toronto, McGill University (Author)
  • Birgit Zatschler - , Chair of Nuclear Physics (Author)
  • Thorsten R. Doeppner - , University of Duisburg-Essen (Author)
  • Jürgen Hescheler - , University of Cologne (Author)
  • Daniel J. Müller - , University of Toronto (Author)
  • R. Loch Macdonald - , University of Toronto (Author)
  • Frauke V. Härtel - , TUD Dresden University of Technology (Author)

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.

Details

Original languageEnglish
Pages (from-to)98-106
Number of pages9
JournalProgress in Neuro-Psychopharmacology and Biological Psychiatry
Volume67
Publication statusPublished - 3 Jun 2016
Peer-reviewedYes

External IDs

PubMed 26875501

Keywords

ASJC Scopus subject areas

Keywords

  • Adverse effects of lithium, Bipolar disorder, Cerebrovascular autoregulation, Endothelial function, Endothelium, Lithium, Stroke, Vascular autoregulation, Vascular relaxation