title: Effect of AR-13324 on episcleral venous pressure in Dutch belted rabbits.
abstract: OBJECTIVE
  AR-13324 is a potential new drug for the treatment of patients with glaucoma that has been shown to lower intraocular pressure (IOP) by increasing trabecular outflow facility and decreasing aqueous production. The present study tested the hypothesis that AR-13324 also lowers IOP by reducing episcleral venous pressure (EVP).
  
  
  METHODS
  In Dutch Belted (DB) rabbits (n=11), arterial pressure (AP), IOP, carotid blood flow (BFcar), heart rate (HR), and EVP were measured invasively. Animals were dosed with AR-13324 (0.04%, topical, n=6) once daily for 3 days. On day 3, the animals were anesthetized, and then, measurements were obtained before dosing with AR-13324 or vehicle (n=5) and for 3 h after dosing. The data (mean±standard error of the mean) were analyzed by repeated measures ANOVA with post hoc testing. Retrospective baseline data from prior similar studies in New Zealand White rabbits were also compiled.
  
  
  RESULTS
  Baseline values were as follows: AP, 101±3 mmHg; IOP; 33±3 mmHg; EVP, 16±1 mmHg; BFcar, 41±4 mL/min; and HR, 330±6 bpm. Three hours after AR-13324 dosing, IOP was reduced by 39%±7% (P<0.001) and EVP decreased by 35%±4% (P<0.05); after vehicle dosing, IOP was reduced by 24%±4% (P<0.05) and EVP increased by 25%±5% (P<0.05). AP, BFcar, and HR were unchanged.
  
  
  CONCLUSIONS
  AR-13324 produces statistically significant lowering of EVP in DB rabbits. In addition, the baseline values for AP, IOP, EVP, BFcar, and HR in the DB rabbit are higher than those previously reported in the New Zealand rabbit.
authors.affiliation: 1 Department of Ophthalmology, University of Texas Health Science Center at San Antonio , San Antonio, Texas.
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Kiel
authors.forename: Casey C
authors.initials: CC
authors.lastname: Kopczynski
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001565:Benzoates / Q000494:pharmacology*; D007429:Intraocular Pressure / Q000187:drug effects*; D008297:Male; D023421:Models, Animal; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000378:metabolism; D011817:Rabbits; D012590:Sclera / Q000098:blood supply* / Q000187:drug effects; D014690:Venous Pressure / Q000187:drug effects*; D015091:beta-Alanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors
chemical_list: D000959:Antihypertensive Agents; D001565:Benzoates; D050484:Norepinephrine Plasma Membrane Transport Proteins; D015091:beta-Alanine; D054460:rho-Associated Kinases; C000603944:netarsudil