Abstract
Purpose: :
Previous studies have shown that the glutamate agonist N-metyl-D-aspartic acid, NMDA, induces a dose-dependent vasorelaxation of pre-constricted porcine retinal arterioles when surrounded by the perivascular retina. However, it is unknown whether other than NMDA glutamate receptors are involved in this vasorelaxation.
Methods: :
Porcine retinal arterioles with preserved perivascular retinal tissue were mounted in a wire myograph for isometric force measurements. After constriction of the arterioles with U46619, a thromboxane analogue, the vasodilating effects of L-glutamic acid combined with antagonists to respectively the NMDA-, metabotropic, and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-/kinate glutamat receptors were studied. In each experiment the perivascular retinal tissue was removed, and the experiment was repeated on the isolated arteriole.
Results: :
L-glutamic acid induced a dose-dependent vasorelaxation, p<0.001 repeated measures ANOVA, (EC50=118.62 µM), which disappeared when the perivascular retina was removed. The NMDA receptor blocker, DL-APV, caused a significant reduction of L-glutamic acid induced vasorelaxation (p=0.033 and 0.048 at 10-3 and 3 x 10-3 M concentrations, respectively), whereas no effect on the glutamate induced vasorelaxation was induced by neither the metabotropic antagonist MCPG (p≥0.1) nor the AMPA / kinate receptor antagonist CNQX (p≥0.11).
Conclusions: :
The findings suggest that the vasorelaxing effect of L-glutamic acid on pre-constricted porcine retinal arterioles in vitro depends on the perivascular retinal tissue and is mediated through a direct action on the glutamate NMDA receptor, but not metabotropic or AMPA/kinate receptors.The findings contributes to the understanding of the tone regulation of retinal arterioles and may potentially help identifying mechanisms for controlling perfusion disturbances in retinal vascular disease.
Keywords: retina: neurochemistry • blood supply • glia