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.