Prostaglandin E2, a Postulated Mediator of Neurovascular Coupling, at Low Concentrations Dilates Whereas at Higher Concentrations Constricts Human Cerebral Parenchymal Arterioles
There is considerable controversy regarding the vasoactive action of prostaglandin E2 (PGE2). On the one hand, indirect evidence implicates that astrocytic release of PGE2 contributes to neurovascular coupling responses mediating functional hyperemia in the brain. On the other hand, overproduction of PGE2 was also reported to contribute to cerebral vasospasm associated with subarachnoid hemorrhage. The present study was conducted to resolve this controversy by determining the direct vasoactive effects of PGE2 in resistance-sized human cerebral parenchymal arterioles. To achieve this goal PGE2-induced isotonic vasomotor responses were assessed in parenchymal arterioles isolated from fronto-temporo-parietal cortical tissues surgically removed from patients and expression of PGE2 receptors were examined. In functionally intact parenchymal arterioles lower concentrations of PGE2 (from 10-8 to 10-6 mol/l) caused significant, endothelium-independent vasorelaxation, which was inhibited by the EP4 receptor blocker BGC201531. In contrast, higher concentrations of PGE2 evoked significant EP1-dependent vasoconstriction, which could not be reversed by the EP4 receptor agonist CAY10598. We also confirmed previous observations that PGE2 primarily evokes constriction in intracerebral arterioles isolated from R. norvegicus. Importantly, vascular mRNA and protein expression of vasodilator EP4 receptors was significantly higher than that of vasoconstrictor EP1 receptors in human cerebral arterioles. PGE2 at low concentrations dilates whereas at higher concentrations constricts human cerebral parenchymal arterioles. This bimodal vasomotor response is consistent with both the proposed vasodilator role of PGE2 during functional hyperemia and its putative role in cerebral vasospasm associated with subarachnoid hemorrhage in human patients.
Czigler, A., Toth, L., Szarka, N., Szilágyi, K., Kellermayer, Z., Harci, A., Vecsernyes, M., Ungvari, Z., Szolics, A., Koller, A., Buki, A., & Toth, P. (2020). Prostaglandin E2, a Postulated Mediator of Neurovascular Coupling, at Low Concentrations Dilates Whereas at Higher Concentrations Constricts Human Cerebral Parenchymal Arterioles. Prostaglandins & Other Lipid Mediators, 146, 106389-106389. https://doi.org/10.1016/j.prostaglandins.2019.106389