Effect of dipyridamole on vascular responses of porcine ciliary arteries.
This study investigated the effects of dipyridamole in isolated porcine ciliary arteries (diameter 200-250 microns). Isolated porcine ciliary arteries were suspended in myograph chambers filled with modified Krebs-Ringer solution (37 degrees C; 95% O2/5% CO2) for isometric tension recording. Dipyridamole induced concentration-dependent relaxations of porcine ciliary arteries with endothelium precontracted with thromboxane analogue U-46619 (10(-6)M), KCl (50 mM), or endothelin-1 (10(-8)M). Removal of the endothelium of the ciliary vessels and preincubation of the arteries with L-NAME (10(-5)M), or indomethacin (10(-5)M), or the combination of the two drugs significantly reduced the relaxation to dipyridamole (p = 0.002-0.03). Similar vascular responses could be observed in a time-dependent analysis of the effect of a single concentration dipyridamole (10(-4)M). The stimulator of cAMP forskolin also caused relaxations. Endothelin-1 (10(-12)-10(-7)M) and U-46619 (10(-10)-10(-6)M) induced potent contractions of porcine ciliary arteries. Preincubation with dipyridamole (10(-5)M) reduced contractions to endothelin-1 as compared to control (p < 0.004), while contractions to U-46619 were only slightly affected under these conditions (n.s.). These findings demonstrate that dipyridamole is a vasodilator in porcine ciliary arteries. Endothelial nitric oxide and prostacyclin contribute importantly to the effects of dipyridamole. Further studies are required to show whether these properties of dipyridamole may also occur in vivo and offer clinical use in patients with ocular vasospasms and other ophthalmic vascular dysfunctions.
Meyer
P
P
Department of Research, University Eye Hospital, Basel, Switzerland.
Flammer
J
J
Lüscher
T F
TF
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002924:Ciliary Body / Q000098:blood supply / Q000187:drug effects*; D005576:Colforsin / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004176:Dipyridamole / Q000494:pharmacology*; D016232:Endothelins / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D013552:Swine; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
D016861:Cyclooxygenase Inhibitors; D016232:Endothelins; D004791:Enzyme Inhibitors; D011450:Prostaglandin Endoperoxides, Synthetic; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D005576:Colforsin; D013928:Thromboxane A2; D004176:Dipyridamole; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D001120:Arginine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin