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Chymase is a chymotrypsin-like serine protease that is stored exclusively in the secretory granules of mast cells and converts big endothelins to endothelin-1 (1-31). The aim of this study was to evaluate the effect of chymase on intraocular pressure in rabbits. Chymase injection (3 and 10 mU) resulted in a trend toward increased intraocular pressure and a significant increase in intraocular pressure at a dose of 10 mU compared with the control. A specific chymase inhibitor, Suc-Val-Pro-PheP (OPh)2 , attenuated the ocular hypertension induced by chymase. Endothelin-1 (1-31) also caused ocular hypertension, which was inhibited by a selective endothelin ETA receptor antagonist, cyclo(D-Asp-Pro-D-Val-Leu-D-Trp) (BQ-123). Moreover, chymase-induced ocular hypertension was inhibited by BQ-123. These results suggest that chymase influences the regulation of intraocular pressure, and it is likely that the formation of endothelin-1 (1-31) and subsequent activation of endothelin ETA receptors are involved in the development of ocular hypertension induced by chymase.
Dr. T. Konno, Drug Research Section II, Fukushima Research Laboratories, TOA EIYO Ltd., 1 Tanaka, Yuno, Iizaka-machi, Fukushima City, Fukushima 960-0280, Japan
5 Experimental glaucoma; animal models
3.8 Pharmacology (Part of: 3 Laboratory methods)