Prostaglandin E2, a postulated astrocyte‐derived neurovascular coupling agent, constricts rather than dilates parenchymal arterioles

Abstract

Prostaglandin E2 (PGE2) is proposed to be released from astrocytic endfeet to dilate parenchymal arterioles through activation of prostanoid (EP4) receptors during neurovascular coupling. However, the direct effects of PGE2 on isolated parenchymal arterioles have not been tested. Particularly, PGE2 is the most versatile of the prostaglandins because of four different receptors subtypes linked to opposing pathways in smooth muscle cells. Here, we examined the effects of PGE2 on the diameter of isolated pressurized parenchymal arterioles from rat and mouse brain. Contrary to the prevailing assumption, we found that PGE2 (0.1, 1 and 5 μmol/L) constricted (11.7%, 18.6% and 34.3%, respectively) rather than dilated parenchymal arterioles. Vasoconstriction to PGE2 was prevented by inhibitors of EP1 receptors. These results strongly argue against a direct role of PGE2 on arterioles during neurovascular coupling. Supported by AHA 09POST2290090 (FD), the NIH R37DK053832, PO1 HL095488, RO1HL44455, RO1HL58231, the Totman Trust for Medical Research and the Fondation Leducq for the Transatlantic Network of Excellence on the Pathogenesis of Small Vessel Disease of the Brain.