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K.H. Jensen, A. Hessellund, C. Aalkjær, J.D. C. Lambert, T. Bek; The Impairment of Retinal Vasoconstriction Caused by Perivascular Tissue Can Be Blocked by Inhibition of the Glutamate NMDA Receptor and COX . Invest. Ophthalmol. Vis. Sci. 2005;46(13):3903.
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Purpose: An elucidation of the basic pathophysiological mechanisms underlying tone regulation in retinal arterioles can be done by in vitro studies of arterioles with attached surrounding retinal tissue. However, previous studies have shown that the presence of perivascular tissue causes the retinal arterioles to be less responsive to vasoconstrictors. Therefore, in order to interpret studies of retinal vascular tone regulation, it is important to elucidate the physiological role of this phenomenon. Methods: Porcine retinal arterioles (diameter ∼ 150 µm, length ∼ 1.8 mm) with a 2 mm patch of adjacent tissue on each side of the vessels were mounted in a small vessel wire myograph for isometric tone measurements. Dose–response experiments were carried out with the vasoconstrictor U46619 in seven concentration steps between 1.0E–9 M and 3.0E–6 M before and after removal of the perivascular retina, and it was tested whether the response was affected by the glutamate receptor subtype agonist NMDA (100 µM, n=7), the NMDA antagonist DL–APV (50 µM, n=32), and the non–selective COX inhibitor Ibuprofen (10 µM, n=16). Results: The presence of retinal tissue impaired the contractile effect of U46619. This impairment was eliminated by blocking the glutamate NMDA receptor (p<0.01) and by inhibition of COX (p<0.01), but could be reversed by NMDA (p<0.01). Conclusions: In vitro studies of tone regulation in retinal arterioles should take into account that the results may be affected by vasocrine substances released from the surrounding retina. The contractile effect of U46619 is decreased by a pathway that involves the glutamate receptor subtype NMDA and COX.
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