Levosimendan is a novel calcium sensitizer that is an established treatment for congestive heart failure. In
coronary vessels, levosimendan has a vasorelaxant, endothelium-independent effect and an antagonistic effect on
endothelin-1 (ET-1). There is also some data for a neuroprotective effect in a traumatic brain injury model, and
levosimendan can prevent the reduction of the luminal area of the basilar artery. We considered that patients who suffer
heart attack after subarachnoid hemorrhage (SAH) might respond well to levosimendan, which might also be useful to
induce hypertension in patients with cerebral vasospasm.
However, the functional effects of levosimendan in the cerebrovasculature are unknown. Here, we investigated the
functional role of levosimendan on rat basilar artery by assessing vasocontractile reactivity in response to ET-1,
sarafotoxin S6c, acetylcholine, sodium nitroprusside, cGMP, and prostaglandin F2α (PGF).
Contrary to observations in coronary vessels, levosimendan did not affect the ET-1 system in cerebral arteries; neither
ET(A)-receptor-induced contraction nor ET(B)-receptor-dependent relaxation were changed. For the nitric oxide (NO)
pathway, only a slight increase was detected. Rather, levosimendan caused significant and dose-dependent relaxation after
To our knowledge, this is the first report that describes levosimendan-induced functional changes of cerebrovascular
contractility and relaxation. Under physiological conditions, levosimendan did not influence ET(A)/ET(B)-receptor
signaling or the NO pathway. Interestingly, levosimendan seemed to affect the prostaglandin system and dosedependently
reversed PGF- induced contraction. We did not detect a vasospastic potential for levosimedan in cerebral
arteries, suggesting that it would be safe for use in SAH patients.