The relaxing effect of perivascular tissue on porcine retinal arterioles in vitro is mimicked by N-methyl-D-aspartate and is blocked by prostaglandin synthesis inhibition.
OBJECTIVE
Retinal hyperperfusion resulting from disturbances in the regulation of arteriolar tone is involved in the pathophysiology of a variety of retinal diseases. The mechanisms underlying this regulation of tone involve cellular components in both the vascular wall and the perivascular tissue. However, previous in vitro studies of the influence of perivascular retinal tissue on retinal tone regulation have been hampered by the release of an endogenous relaxing factor that renders the arteriole insensitive to vasoconstrictors. The purpose of the present study was to test whether N-methyl-D-aspartate (NMDA) and gamma-amino butyric acid (GABA) receptors, and a cyclooxygenase (COX) product influence this effect of perivascular retinal tissue in vitro.


METHODS
Porcine retinal arterioles were mounted in a wire myograph for isometric force measurements. The contractile effect of the prostaglandin analogue U46619 was studied on vessels with preserved perivascular retinal tissue and after this tissue had been removed. The influence of the perivascular tissue was studied after addition of NMDA (a specific agonist for a subtype of the glutamate receptor), DL-amino-5-phosphonovaleric acid (DL-APV, an antagonist at the same receptor), the natural inhibitory transmitter GABA, and picrotoxin (an antagonist at ionotropic GABA receptors). These experiments were made in the absence and presence of the COX inhibitor, ibuprofen.


RESULTS
U46619 caused a concentration-dependent contraction of isolated retinal arterioles. This vasoconstriction was significantly smaller in the presence of perivascular tissue. The NMDA-receptor antagonist, DL-APV, reduced this attenuating influence of the perivascular tissue on the response to U46619, and the response could be modified by NMDA and GABA, but not by picrotoxin. However, ibuprofen totally blocked the attenuating influence of the perivascular tissue on the response to U46619.


CONCLUSIONS
The inhibition of vascular contractility induced by perivascular retinal tissue in vitro involves NMDA-receptors and an effect of GABA-mimetic substance on retinal tissue. The generation of these effects involves a COX product.
Holmgaard
Kim
K
Department of Ophthalmology, Arhus University Hospital, Arhus, Denmark. khj@akhphd.au.dk
Aalkjaer
Christian
C
Lambert
John D C
JD
Hessellund
Anders
A
Bek
Toke
T
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000008:administration & dosage / Q000494:pharmacology; D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D016202:N-Methylaspartate / Q000494:pharmacology*; D011448:Prostaglandin Antagonists / Q000494:pharmacology*; D012160:Retina / Q000502:physiology*; D012171:Retinal Vessels / Q000187:drug effects* / Q000502:physiology*; D013552:Swine; D014661:Vasoconstriction / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000494:pharmacology; D014664:Vasodilation / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D011448:Prostaglandin Antagonists; D014662:Vasoconstrictor Agents; D005680:gamma-Aminobutyric Acid; D016202:N-Methylaspartate; D015763:2-Amino-5-phosphonovalerate; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid