A differential impact of lithium on endothelium-dependent but not on endothelium-independent vessel relaxation
Research output: Contribution to journal › Research article › Contributed › peer-review
Contributors
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 language | English |
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Pages (from-to) | 98-106 |
Number of pages | 9 |
Journal | Progress in Neuro-Psychopharmacology and Biological Psychiatry |
Volume | 67 |
Publication status | Published - 3 Jun 2016 |
Peer-reviewed | Yes |
External IDs
PubMed | 26875501 |
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Keywords
ASJC Scopus subject areas
Keywords
- Adverse effects of lithium, Bipolar disorder, Cerebrovascular autoregulation, Endothelial function, Endothelium, Lithium, Stroke, Vascular autoregulation, Vascular relaxation