Pericytes are present tight around the intervals of capillaries, play an essential role in stabilizing the blood-brain barrier, regulating blood flow and
immunomodulation, and persistent contraction of pericytes eventually leads to impaired blood flow and poor clinical outcomes in
ischemic stroke. We previously show that
iptakalim, an
ATP-sensitive
potassium (K-
ATP) channel opener, exerts protective effects in neurons, and glia against
ischemia-induced injury. In this study we investigated the impacts of
iptakalim on pericytes contraction in
stroke. Mice were subjected to cerebral artery occlusion (MCAO), then administered
iptakalim (10 mg/kg, ip). We showed that
iptakalim administration significantly promoted recovery of cerebral blood flow after
cerebral ischemia and reperfusion. Furthermore, we found that
iptakalim significantly inhibited pericytes contraction, decreased the number of obstructed capillaries, and improved cerebral microcirculation. Using a
collagen gel contraction assay, we demonstrated that cultured pericytes subjected to
oxygen-
glucose deprivation (OGD) consistently contracted from 3 h till 24 h during reoxygenation, whereas
iptakalim treatment (10 μM) notably restrained pericyte contraction from 6 h during reoxygenation. We further showed that
iptakalim treatment promoted K-
ATP channel opening via suppressing SUR2/EPAC1 complex formation. Consequently, it reduced
calcium influx and ET-1 release. Taken together, our results demonstrate that
iptakalim, targeted K-
ATP channels, can improve microvascular disturbance by inhibiting pericyte contraction after
ischemic stroke. Our work reveals that
iptakalim might be developed as a promising pericyte regulator for treatment of
stroke.