Vasoactive responses of U46619, PGF2alpha, latanoprost, and travoprost in isolated porcine ciliary arteries.
OBJECTIVE
To compare the vasoactive properties of the prostanoids U46619 (thromboxane A2 analogue), prostaglandin F(2alpha) (PGF(2alpha)), latanoprost free acid, and travoprost free acid in isolated porcine ciliary arteries.


METHODS
In a myograph system (isometric force measurement), quiescent vessels were exposed (cumulatively) to U46619, PGF(2alpha), latanoprost, or travoprost (0.1 nM-0.1 mM). Experiments were also conducted in the presence of SQ 29548 (TP-receptor antagonist; 3-10 microM) or AL-8810 (FP-receptor antagonist; 3-30 microM). Contractions were expressed as the percentage of 100 mM potassium chloride-induced contractions.


RESULTS
In quiescent vessels, contractions (concentration-response curves) induced by (0.1 mM) PGF(2alpha) (87.9% +/- 3.5%), U46619 (66.7% +/- 4.1%), and latanoprost (62.9% +/- 3.6%) were more pronounced (P < or = 0.001) than those induced by travoprost (23.0% +/- 4.4%). Concentration-response curves for PGF(2alpha), latanoprost, and travoprost were preceded by a smaller contraction peak (0.1 microM) that was higher (P < or = 0.05) for travoprost (24.4% +/- 2.8%) than for PGF(2alpha) (12.9% +/- 4.6%), but not different (P = 0.58) from latanoprost (22.0% +/- 3.0%). The 50% maximal contraction (PD50: negative log M concentration) of U46619 (-8.05 +/- 0.13) was lower (P < or = 0.001) than those of latanoprost (-5.65 +/- 0.10), PGF(2alpha) (-5.49 +/- 0.14), and travoprost (-5.12 +/- 0.52). Contractions were inhibited (P < or = 0.05-0.001) either by SQ 29548 or AL-8810.


CONCLUSIONS
In isolated porcine ciliary arteries, all prostanoids tested induced contractions. Among them, travoprost appeared to be the least potent and U46619 the most efficient.
Vysniauskiene
Ineta
I
Laboratory of Pharmacology and Physiology, University Eye Clinic, Basel, Switzerland.
Allemann
Reto
R
Flammer
Josef
J
Haefliger
Ivan O
IO
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology*; D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic; D019842:Ciliary Arteries / Q000187:drug effects* / Q000502:physiology; D003008:Cloprostenol / Q000031:analogs & derivatives* / Q000494:pharmacology; D015237:Dinoprost / Q000031:analogs & derivatives / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines / Q000494:pharmacology; D000077338:Latanoprost; D011461:Prostaglandins F, Synthetic / Q000494:pharmacology*; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors; D013552:Swine; D000069557:Travoprost; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D019086:Bridged Bicyclo Compounds, Heterocyclic; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D011461:Prostaglandins F, Synthetic; D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; D014662:Vasoconstrictor Agents; C121227:AL 8810; D003008:Cloprostenol; D000077338:Latanoprost; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; C045749:SQ 29548; D015237:Dinoprost; D000069557:Travoprost