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1 Department of Ophthalmology, Showa University, Tokyo, Japan; Pharmacology & Therapeutics, University of Florida, Gainesville, Florida, United States
2 Institute of Regenerative Medicine, Wake Forest University, Winston-Salem, North Carolina, United States; Pharmacology & Therapeutics, University of Florida, Gainesville, Florida, United States
3 UNIVERSITY OF FL-ENDOCRINOLOGY; UNIVERSITY OF FL-ENDOCRINOLOGY, United States; Pharmacology & Therapeutics, University of Florida, Gainesville, Florida, United States
4 Pharmacology & Therapeutics, University of Florida, Gainesville, Florida, United States; Institute of Regenerative Medicine, Wake Forest University, Winston-Salem, North Carolina, United States; Danish Myotechnology, Aarhus, Denmark
* To whom correspondence should be addressed. E-mail: yjarajap{at}wfubmc.edu.
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 mm Hg of intraluminal pressure. Arteries maintained almost similar diameter over the range of pressures 50-210 mm Hg and forced dilatation was observed at pressures >210 mm Hg. Denudation of endothelium increased the sensitivity of arteries to pressure-induced constriction and significantly higher myogenic tone was observed in the pressure range of 10-100 mm Hg. Indomethacin and COX-2 inhibition by SC236 decreased myogenic tone whereas COX-1 inhibition by SC560 potentiated myogenic tone in lower concentration range and decreased at higher concentration. Pressure-induced constriction was completely blocked by 1 µM nifedipine. Phospholipase C (PLC) 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 mm Hg. Rho-kinase inhibition by Y-27632 (30 µM) and HA 1077 (30 µM) decreased myogenic tone by 75 and 73%, respectively, and 1 microM 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 PLC-activation to myogenic tone is minimal while Rho-kinase activation plays a predominant role in the myogenic reactivity in this artery.
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