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Endothelium-dependent regulation of the ophthalmic microcirculation in the perfused porcine eye: role of nitric oxide and endothelins.

Abstract：

PURPOSE:The endothelium produces nitric oxide and endothelin (ET). This study was designed to investigate the endothelium-dependent regulation of the porcine ophthalmic microcirculation. METHODS:Isolated porcine eyes were perfused with a modified Langendorff setup (Hugo Sachs Elektronik KG, Freiburg, Germany) at a perfusion pressure of 80 cm H2O with Krebs-Ringer bicarbonate solution (37 degrees C; 95% O2, 5% CO2). RESULTS:The inhibitor of nitric oxide formation, L-nitroarginine methylester (L-NAME; 10(-6) to 10(-4) M), evoked decreases in flow (maximal decrease, 39% +/- 6%; P < 0.005 versus control). The endothelium-dependent vasodilator bradykinin evoked increases in ophthalmic flow (maximal increase, 26% +/- 2%; P < 0.05 versus control) prevented by L-NAME. The effect of endothelin-1 (ET-1; 10(-12) to 10(-11) M) on flow was biphasic, with early vasodilation (1 to 2 minutes) and late vasoconstriction. At 10(-12) M, the increase in flow was most pronounced (24% +/- 5%; P < 0.05 versus control), whereas 10(-10) M caused only significant decreases in flow (59% +/- 5%; P < 0.001 versus control). Endothelin-3 (ET-3) evoked similar vasodilator effects as ET-1 but less vasoconstriction. The vasodilator effects of ET-3 were prevented by pretreatment of the eye with indomethacin (10(-5) M, to block the production of prostaglandins; P < 0.05 versus control). The endothelinA receptor antagonist FR-139317 significantly reduced vasoconstriction to ET-1 (10(-10) M; P < 0.001 versus control). The thromboxane analogue (U-46619) reduced flow in a concentration-dependent manner (P < 0.001 versus control). CONCLUSIONS:Endothelium-derived nitric oxide released under basal conditions or stimulated by bradykinin significantly regulated flow to the porcine ophthalmic microcirculation. This vasodilator system may play an important protective role against vasospasm. In contrast, ET-1 has vasodilator effects through the release of prostaglandins and potent vasoconstrictor properties mediated through ETA receptors.

journal_name

Invest Ophthalmol Vis Sci

journal_title

Investigative ophthalmology & visual science

authors

Meyer P,Flammer J,Lüscher TF

subject

Has Abstract

pub_date

1993-12-01 00:00:00

pages

3614-21

issue

eissn

0146-0404

issn

1552-5783

journal_volume

pub_type

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Endothelium-dependent regulation of the ophthalmic microcirculation in the perfused porcine eye: role of nitric oxide and endothelins.