Key result
Intravitreal indomethacin and PF-04418948 suppress nitric oxide-induced retinal arteriolar dilation in rats.
Why the study?
Although NO-induced glial cell vasodilation involves prostaglandins, the specific prostaglandin types and prostanoid receptors mediating this response were not clear.
p-value: p=<0.05
Activation of the arachidonic acid cascade and subsequent stimulation of prostanoid EP2 receptors by glial cell-derived PGE2 play an important role in NO-induced retinal vasodilatory mechanisms.
Supports EP2 role in rat retinal NO vasodilation; leaves open translation to human ocular disease or therapy.
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.
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Mori et al. (2022) studied Healthy (retinal vasodilation model) (n=44). PF-04418948 (prostanoid EP2 receptor antagonist) and Indomethacin vs. Vehicle was evaluated on Change in retinal arteriolar diameter induced by intravitreal administration of NOR3 (NO donor) (p=<0.05). Intravitreal pretreatment with the cyclooxygenase inhibitor indomethacin and the prostanoid EP2 receptor antagonist PF-04418948 significantly suppressed nitric oxide-induced retinal arteriolar dilation in rats.
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