title: Effects of Rho-associated protein kinase inhibitors Y-27632 and Y-39983 on isolated rabbit ciliary arteries.
abstract: OBJECTIVE
  In normotensive eyes, reduced ocular blood flow can lead to glaucoma pathogenesis. Drugs that reduce intraocular pressure (IOP) often cause vasodilation of the ciliary arteries and improve blood flow to the eye. A novel class of drugs called Rho-associated coiled coil-forming protein kinase (ROCK) inhibitors can lower IOP. Therefore, we tested the ability of two ROCK inhibitors, Y-27632 and Y39983, to relax rabbit ciliary arteries.
  
  
  METHODS
  We measured in vitro ciliary artery smooth muscle contractions by isometric tension recordings and changes of intracellular free calcium concentration ([Ca(2+)](i)) by fluorescence photometry.
  
  
  RESULTS
  Both Y-27632 and Y-39983 induced a concentration-dependent relaxation in rabbit ciliary arteries precontracted with a high-potassium (high-K) solution. The amplitude of relaxation induced by Y-27632 and Y-39983 was not affected by either 100 μM N (G)-nitro-L: -arginine methyl ester (L: -NAME) or 10 μM indomethacin. In Ca(2+)-free solution, Y-27632 and Y-39983 significantly inhibited the transient contraction of ciliary arteries induced by 10 μM histamine. However, neither Y-27632 nor Y-39983 affected the elevation of [Ca(2+)](i) induced by high-K solution and histamine.
  
  
  CONCLUSIONS
  We concluded that Y-27632 and Y-39983 relaxed isolated rabbit ciliary artery segments in vitro. The mechanism of relaxation was not dependent on endothelial-derived factors such as nitric oxide (NO) or prostacyclin, nor was it dependent on changes in intracellular Ca(2+) concentration.
authors.affiliation: Department of Ophthalmology, Akita University School of Medicine, 1-1-1 Hondo, Akita, Japan. watabe@med.akita-u.ac.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Watabe
authors.affiliation: Department of Ophthalmology, Akita University School of Medicine, 1-1-1 Hondo, Akita, Japan.
authors.forename: Sanae
authors.initials: S
authors.lastname: Abe
authors.affiliation: Department of Ophthalmology, Akita University School of Medicine, 1-1-1 Hondo, Akita, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yoshitomi
mesh_terms: D000577:Amides / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D019842:Ciliary Arteries / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D015590:Fluorophotometry; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology*; D011817:Rabbits; D014664:Vasodilation / Q000502:physiology*; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors*
chemical_list: D000577:Amides; D011725:Pyridines; C520365:Y-39983; C108830:Y 27632; D054460:rho-Associated Kinases; D002118:Calcium; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin