K ATP channels in cerebral hemodynamics: a systematic review of preclinical and clinical studies

Cumulative evidence suggests that ATP-sensitive potassium (K ) channels act as a key regulator of cerebral blood flow (CBF). This implication seems to be complicated, since K channels are expressed in several vascular-related structures such as smooth muscle cells, endothelial cells and pericytes. In this systematic review, we searched PubMed and EMBASE for preclinical and clinical studies addressing the involvement of K channels in CBF regulation. A total of 216 studies were screened by title and abstract. Of these, 45 preclinical and 6 clinical studies were included. Preclinical data showed that K channel openers (KCOs) caused dilation of several cerebral arteries including pial arteries, the middle cerebral artery and basilar artery, and K channel inhibitor (KCI) glibenclamide, reversed the dilation. Glibenclamide affected neither the baseline CBF nor the baseline vascular tone. Endothelium removal from cerebral arterioles resulted in an impaired response to KCO/KCI. Clinical studies showed that KCOs dilated cerebral arteries and increased CBF, however, glibenclamide failed to attenuate these vascular changes. Endothelial K channels played a major role in CBF regulation. More studies investigating the role of K channels in CBF-related structures are needed to further elucidate their actual role in cerebral hemodynamics in humans. Prospero: CRD42023339278 (preclinical data) and CRD42022339152 (clinical data).