The general anesthetic isoflurane inhibits calcium activity in cerebrovascular endothelial cells and disrupts vascular tone

Abstract

Calcium signaling in cerebrovascular endothelial cells (CVECs) has been identified to play key physiological and pathological roles in blood brain barrier function and neurovascular coupling, which involve dynamic changes in vessel diameter. However, there are no studies that measured correlated changes in vessel diameter and calcium activity in CVECs in vivo. In this study, we used the general anesthetic isoflurane (ISO) to induce a maximally dilated state in cortical blood vessels and measured the effects of the manipulation on CVEC calcium reporter activity in awake Cdh5BAC-GCaMP mice by use of two-photon fluorescence microscopy through thinned skull cranial windows. For the first time, we report dual effects of ISO on calcium activity in cerebral blood vessels of different diameter. During anesthesia induction ISO exposure triggered a short latency synchronous increase in calcium activity, followed by a period of activity suppression in small, medium, and large diameter vessels. Furthermore, during anesthesia maintenance calcium activity was desynchronized, and the relationship between vascular tone and calcium activity was disrupted in all vessel types. Based on these results we propose that there is a feedback mechanism between intracellular calcium fluctuations in CVECs and the maintenance of cerebrovascular tone.

Blood Vessels as a Key Mediator for Ethanol Toxicity: Implication for Neuronal Damage

“…The ethanol-binding proteins stated above are mainly expressed in neurons and glial cells, and there is currently no knowledge of membrane ethanol-binding proteins on endothelial cells. However, some studies have reported the potentially direct action of volatile isoflurane on endothelial cells [68][69][70]. This may indicate the existence of an ethanol "receptor" on endothelial cells, which should be characterized in future studies.…”