Effects of calcium channel blockers on the response to endothelin-1, bradykinin and sodium nitroprusside in porcine ciliary arteries.
Calcium channel blockers are increasingly used in ophthalmology, for instance in patients with visual field defects caused by vasospasm. Endothelin is a new vasoactive peptide which also has been implicated in hypoperfusion of the ophthalmic circulation. This study investigated the effects of the calcium channel blockers on the response to endothelin-1, bradykinin and sodium nitroprusside in isolated porcine ciliary arteries (diameter 200-250 microns). Isolated porcine ciliary arteries were suspended in myograph systems filled with modified Krebs-Ringer solution (37 degrees C; 95% O2/5% CO2) for isometric tension recording. Endothelin-1 (10(-12) -10(-7) M) induced potent concentration-dependent contractions of porcine ciliary arteries (PD50 = 8.3 +/- 0.1; n = 7). Lacidipine (10(-5) -10(-7) M) and nifedipine (10(-5) M) significantly reduced the contractions and decreased the sensitivity to endothelin-1 as compared to control (P < 0.03). On the other hand, endothelium-dependent relaxations to bradykinin (10(-10) -10(-6) M) and endothelium-independent relaxations to sodium nitroprusside (10(-10) -10(-4) M) remained unaffected by the calcium channel blocker. These findings demonstrate that in porcine ciliary arteries, the calcium channel blockers selectively inhibit endothelin-1-induced contractions, while leaving endothelium-dependent and endothelium-independent relaxations unaffected. This property of calcium channel blockers may contribute to the clinical efficacy of this class of drugs in patients with ocular vasospasms.
Meyer
P
P
Department of Research, University Eye Hospital, Basel University Hospital, Inselspital, Bern, Switzerland.
Lang
M G
MG
Flammer
J
J
Lüscher
T F
TF
D000818:Animals; D001158:Arteries / Q000187:drug effects; D001920:Bradykinin / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002924:Ciliary Body / Q000098:blood supply*; D004095:Dihydropyridines / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D016232:Endothelins / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects; D066298:In Vitro Techniques; D009543:Nifedipine / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology*; D013552:Swine; D014661:Vasoconstriction / Q000187:drug effects*
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D016232:Endothelins; D009599:Nitroprusside; C060285:lacidipine; D009543:Nifedipine; D001920:Bradykinin