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1Department of Pharmacology and Therapeutics, University of Florida, Gainesville, Florida; 2Wake Forest Institute of Regenerative Medicine, Wake Forest University, Winston-Salem, North Carolina; 3Department of Ophthalmology, College of Medicine, Showa University, Tokyo, Japan; and 4Danish MyoTechnology, Aarhus, Denmark
Submitted 13 June 2006 ; accepted in final form 15 August 2006
The pressure-induced constriction in the rat ophthalmic artery was characterized. Ophthalmic arteries were isolated, cannulated in an arteriograph, and pressurized. Arteries developed 25% constriction at 70 mmHg of intraluminal pressure. Arteries maintained almost similar diameter over the range of pressures 50210 mmHg, and forced dilatation was observed at pressures >210 mmHg. Denudation of endothelium increased the sensitivity of arteries to pressure-induced constriction, and significantly higher myogenic tone was observed in the pressure range of 10100 mmHg. Indomethacin and cyclooxygenase-2 inhibition by SC-236 decreased myogenic tone, whereas cyclooxygenase-1 inhibition by SC-560 potentiated myogenic tone in a lower concentration range and decreased at a higher concentration. Pressure-induced constriction was completely blocked by 1 µM nifedipine. Phospholipase C inhibition by 6 µM U-73122 decreased myogenic tone by 39%, whereas PKC inhibitor GF-109203X (3 µM) had no effect. Constriction to phenylephrine was significantly decreased by U-73122 (1 µM) and GF-109203X (3 µM) at an intraluminal pressure of 10 mmHg. Rho-kinase inhibition by Y-27632 (30 µM) and HA-1077 (30 µM) decreased myogenic tone by 75% and 73%, respectively, and 1 µM Y-27632 significantly decreased myogenic tone developed in response to graded increases in pressure. These results suggest that rat ophthalmic artery has an efficient pressure-dependent autoregulatory function that is modulated by endothelium. Contribution of phospholipase C-activation to myogenic tone is minimal, whereas Rho-kinase activation plays a predominant role in the myogenic reactivity in this artery.
endothelium; phospholipase C; rho kinase
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