Abstract
Purpose: :
Disturbances in retinal perfusion due to impaired regulation of vascular tone are believed to be involved in the pathogenesis of a number of vision threatening retinal diseases. In two recent studies, we have shown that the glutamate receptor agonist, N-methyl-D-aspartic acid (NMDA), and adenosine induce relaxation of porcine retinal arterioles in vitro. However, it remains to be elucidated whether the action of the two substances are separate or coupled.
Methods: :
Porcine retinal arterioles with preserved perivascular retinal tissue were mounted in a myograph for isometric tone measurements. Changes in tone were induced by increasing concentrations of NMDA in the presence of blockers of adenosine receptors and of ATP hydrolysis. Additionally, changes in tone were also induced with increasing concentrations of adenosine in the presence of the NMDA receptor blocker, DL-APV. All experiments were repeated after the perivascular tissue had been removed.
Results: :
NMDA produced a concentration-dependent relaxing effect on retinal vessels with preserved perivascular retinal tissue (p<0.001) which disappeared after removal of the perivascular tissue. Blocking of the NMDA receptor, adenosine receptors and hydrolysis of ATP significantly reduced the vasorelaxing effect of NMDA in the presence of perivascular retinal tissue (p<0.05 for all three comparisons). However, adenosine-induced vasorelaxation was not significantly affected after blocking the NMDA receptor with DL-APV, neither on isolated arterioles (p=0.08) nor on arterioles with preserved perivascular tissue (p=0.22). Ibuprofen blocked the vasorelaxing action of NMDA but did not affect the vasorelaxing effect of the other substances tested.
Conclusions: :
The findings suggest that the vasorelaxing effect of NMDA is mediated by hydrolysis of ATP to adenosine in the perivascular retinal tissue.
Keywords: blood supply • retina: neurochemistry • neurotransmitters/neurotransmitter systems