Effects of prostaglandin F(2α) analogues on endothelin-1-induced impairment of rabbit ocular blood flow: comparison among tafluprost, travoprost, and latanoprost.
We investigated the effects of prostaglandin F(2α) (PGF(2α)) analogues on the endothelin-1 (ET-1)-induced impairment of optic nerve head (ONH) blood flow and on ET-1-induced contraction in isolated ciliary artery segments. In male rabbits, one of four PGF(2α) analogues [0.0015% tafluprost, 0.0015% 15-hydroxyl tafluprost (15-OH tafluprost), 0.005% latanoprost, or 0.004% travoprost] was topically administered at various pretreatment times before intravitreal ET-1 injection. ONH blood flow was estimated by the laser speckle method, which expresses blood velocity as a quantitative index, the squared blur rate (SBR). SBR was measured just before (baseline value) and at 30, 60, and 120 min after ET-1 injection. SBR was significantly decreased from 4.47 ± 0.20 to 3.50 ± 0.10 (78.6 ± 2.4% of baseline) at 120 min after intravitreal ET-1 injection (5 pmol/eye). The ET-1-induced decrease was almost completely prevented by tafluprost and significantly inhibited by the other three analogues. The inhibitory effect lasted longest with tafluprost, as indicated by the effective pretreatment times (tafluprost: 90, 120, or 240 min; 15-OH tafluprost: 90, but not 120 or 240 min; latanoprost and travoprost: 120, but not 240 min). In vitro, the effects of PGF(2α) analogues on ET-1-induced contractions in male rabbit ciliary arteries were evaluated using an isometric tension recording system. Tafluprost, latanoprost, travoprost, and 15-OH tafluprost concentration-dependently relaxed the 10 nM ET-1-induced ciliary artery contraction. Improvement of the ocular circulation may be superior with tafluprost than with the other PGF(2α) analogues. The underlying mechanism may involve relaxation of ocular resistance vessels.
Kurashima
Hiroaki
H
Research and Development Center, Santen Pharmaceutical Co. Ltd., Nara, Japan. hiroaki.kurashima@santen.co.jp
Watabe
Hiroshi
H
Sato
Noriko
N
Abe
Sanae
S
Ishida
Naruhiro
N
Yoshitomi
Takeshi
T
D000287:Administration, Topical; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001783:Blood Flow Velocity / Q000187:drug effects; D019842:Ciliary Arteries / Q000502:physiology; D003008:Cloprostenol / Q000031:analogs & derivatives* / Q000494:pharmacology; D015237:Dinoprost / Q000031:analogs & derivatives*; D019332:Endothelin-1 / Q000037:antagonists & inhibitors* / Q000633:toxicity; D007537:Isometric Contraction / Q000187:drug effects; D017078:Laser-Doppler Flowmetry; D000077338:Latanoprost; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D009898:Optic Disk / Q000098:blood supply*; D011460:Prostaglandins F / Q000494:pharmacology*; D011461:Prostaglandins F, Synthetic / Q000494:pharmacology*; D011817:Rabbits; D012039:Regional Blood Flow / Q000187:drug effects; D000069557:Travoprost
D000959:Antihypertensive Agents; D019332:Endothelin-1; D011460:Prostaglandins F; D011461:Prostaglandins F, Synthetic; C485333:tafluprost; D003008:Cloprostenol; D000077338:Latanoprost; D015237:Dinoprost; D000069557:Travoprost