Role of Prostaglandins in Nitric Oxide-Induced Glial Cell-Mediated Vasodilation in Rat Retina

• Published in: Biomolecules
• Main Authors: Asami Mori, Haruka Seki, Satoru Mizukoshi, Takashi Uezono, Kenji Sakamoto
• Format: Article
• Language: English
• Published: MDPI AG 2022-10-01
• Subjects: glial cell; nitric oxide; prostanoid EP₂ receptor; retina
• Online Access: https://www.mdpi.com/2218-273X/12/10/1403

We previously identified that NO derived from neuronal cells acts on glial cells and causes vasodilation in the healthy rat retina via the release of epoxyeicosatrienoic acids (EETs) and prostaglandins (PGs) by activation of the arachidonic acid cascade. However, it is not clear which PG types are involved in these responses. The aim of the present study was to identify prostanoid receptors involved in glial cell-derived vasodilation induced by NO in rat retina. Male Wistar rats were used to examine the effects of intravitreal pretreatment with indomethacin, a cyclooxygenase inhibitor; PF-04418948, a prostanoid EP₂ receptor antagonist; and CAY10441, a prostanoid IP receptor antagonist, on the changes in the retinal arteriolar diameter induced by intravitreal administration of NOR3, an NO donor. Retinal arteriolar diameters were measured using ocular fundus images captured with a high-resolution digital camera in vivo. The increase in the retinal arteriolar diameter induced by intravitreal injection of NOR3 was significantly suppressed by intravitreal pretreatment with indomethacin and PF-04418948, but not by CAY10441. The dose of PF-04418948 and CAY10441 injected intravitreally in the present study significantly reduced the increase in the retinal arteriolar diameter induced by prostaglandin E₂ (PGE₂) and prostaglandin I₂ (PGI₂), respectively. These results suggest that activation of the arachidonic acid cascade and subsequent stimulation of prostanoid EP₂ receptors are involved in rat retinal vasodilatory responses evoked by NO-induced glial cell stimulation. Therefore, glial cell-derived PGE₂, similar to EETs, may play an important role in retinal vasodilatory mechanisms.