Effect of chymase on intraocular pressure in rabbits

• Published in: European journal of pharmacology 2005-11, Vol.524 (1), p.132-137
• Main Authors: Konno, Takashi, Maruichi, Midori, Takai, Shinji, Oku, Hidehiro, Sugiyama, Tetsuya, Uchibori, Takehiro, Nagai, Akihiko, Kogi, Kentaro, Ikeda, Tsunehiko, Miyazaki, Mizuo
• Format: Article
• Language: English
• Subjects: Animals; Antihypertensive Agents - pharmacology; Biological and medical sciences; Chymase; Chymases; Dose-Response Relationship, Drug; Endothelin ET A receptor; Endothelin Receptor Antagonists; Endothelin-1 (1–31); Endothelin-1 - administration & dosage; Endothelin-1 - analogs & derivatives; Enzyme Inhibitors - pharmacology; Humans; Intraocular pressure; Intraocular Pressure - drug effects; Intraocular Pressure - physiology; Male; Medical sciences; Oligopeptides - pharmacology; Peptide Fragments - administration & dosage; Peptides, Cyclic - pharmacology; Pharmacology. Drug treatments; Rabbits; Recombinant Proteins - administration & dosage; Serine Endopeptidases - administration & dosage; Serine Endopeptidases - genetics; Time Factors
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2005.09.048

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-Phe P(OPh) 2, attenuated the ocular hypertension induced by chymase. Endothelin-1 (1–31) also caused ocular hypertension, which was inhibited by a selective endothelin ET A 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 ET A receptors are involved in the development of ocular hypertension induced by chymase.