The vascular effect of glibenclamide: A systematic review

Abstract

Objective: To systematically review the vascular effects of glibenclamide. Background: Infusion of adenosine triphosphate (ATP)-sensitive potassium (KATP) channel opener (KCO) levcromakalim dilates cranial arteries and induces headache and migraine attacks. Recent data show that levcromakalim-induced vasodilation is associated with headache. Glibenclamide is a KATP channel blocker that may alter the vascular tone and thus has an impact on headache or migraine prevention. Methods: A search through PubMed was undertaken for studies investigating the vascular effects of glibenclamide in vitro as well as in vivo published until July 2019. Results: We identified 58 articles; 31 in vitro studies, 24 in vivo studies and 3 studies with both. The main findings were that glibenclamide inhibited levcromakalim-induced and other KCOs-induced vasodilation, while the basal vascular tone remained unchanged. Conclusion: Glibenclamide could inhibit vasodilation by KCOs, and further studies are needed to clarify the vascular effect of glibenclamide on human cranial arteries.

Effect of KATP channel blocker glibenclamide on levcromakalim-induced headache

“…It is tempting to speculate that the increased headache incidence and intensity 180 min after levcromakalim infusion may be associated with the half-life of glibenclamide and thus, the decrease of plasma glibenclamide concentration. Consistent with previous studies investigating effects of 5–10 mg oral glibenclamide on systemic hemodynamic (17,18,20–23), we found no change in HR and MABP after glibenclamide compared to placebo. However, one study reported that oral glibenclamide (10 mg) increased systolic but not diastolic blood pressure compared with placebo (24).…”

“…In preclinical experiments, glibenclamide attenuated potassium channel openers-induced vascular changes without altering the basal vascular tone (23). A few studies have reported that glibenclamide increased the basal tone in rat dural artery (25,26).…”

Cerebrovascular effects of glibenclamide investigated using high-resolution magnetic resonance imaging in healthy volunteers

“…33,34 In preclinical experiments, glibenclamide attenuated KCOs-induced vasodilation without altering the basal vascular tone. 14 Few studies reported that glibenclamide increased the basal tone in rat dural artery, 16,17 and one study reported that glibenclamide had no effect on brain perfusion signals in a rat model of severe ischemia with delayed reperfusion. 6 In the present study, glibenclamide did not alter the in vivo global mean CBF and arterial circumferences.…”

“…Different effects of glibenclamide between pre- and posttreatment cannot be applied as both approaches inhibited KCOs-induced vasodilation in preclinical studies. 14 One possible explanation for the lack of glibenclamide effect on vascular changes could be that glibenclamide has less efficacy on SUR2B subunit expressed in the VSMCs compared to SUR1. Another explanation is that the preclinical studies used a high dose which is not applicable for clinical use.…”

“…9–11 Preclinical studies implicate K ATP channel in the regulation of cerebral blood flow (CBF), 12 , 13 and demonstrate that glibenclamide inhibits K ATP channel-induced vasodilation without altering the basal vascular tone. 14–18 K ATP channel activation may have inherent protective effects during hypoxia and ischemia-induced brain injury. 19 , 20 Effect of glibenclamide on cerebral hemodynamics and on K ATP channel-induced vasodilation in humans is not elucidated.…”