Arachidonate-Induced Dilation of Retinal Arterioles: More Than Meets the Eye

Regulation of retinal blood flow is critical to normal eye function. Retinal arteriolar myogenic tone, determined by the pressure-induced contraction of the smooth muscle cells in the wall of these microvessels, importantly contributes to retinal blood flow regulation. However, the cellular mechanisms involved in the control of retinal arteriolar tone remain to be resolved. While much has been learned from the studies of arteries and arterioles in the periphery, regional heterogeneity in mechanisms involved in the regulation of myogenic tone make extrapolation from one vascular bed to another impossible. The study by Kur et al. ¹ in this issue of IOVS emphasizes this important, but often unappreciated point. Previous studies of the mechanism of action by which arachidonic acid (AA) produces vasodilation have centered on K⁺ channels as the target for the actions of this polyunsaturated fatty acid (PUFA). Kur and associates ¹ clearly show that in retinal arterioles, while AA modulates the function of two dominant K⁺ channels expressed in the smooth muscle cells of these vessels, AA-induced changes in K⁺ channel functions are unlikely to be involved in the mechanism by which this PUFA dilates retinal arterioles. Instead, the authors provide compelling evidence that AA inhibits Ca²⁺ influx through voltage-gated Ca²⁺ channels (VGCCs), which, in turn, decreases the occurrence and properties of Ca²⁺ sparks and Ca²⁺ oscillations to inhibit contraction of the smooth muscle cells producing vasodilation. What remains to be established is the mechanism by which AA inhibits the VGCCs. This study highlights the complexity of mechanisms responsible for regulation of retinal arteriolar tone. The data support the hypothesis that there are substantial regional differences in these mechanisms warranting studies specific to the tissue and vascular branch level of interest. Regional heterogeneity in mechanisms may provide new targets for development of drugs with tissue-specific effects. 

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