title: Effects of BRL 38227, sodium nitroprusside and verapamil on collateral perfusion following acute arterial occlusion in the rabbit isolated ear.
abstract: 1. We have used an isolated, buffer-perfused, rabbit ear model of acute arterial occlusion to investigate the effects of the nitrovasodilator sodium nitroprusside, the potassium channel activator BRL 38227 (the active (-)-enantiomer of cromakalim) and the calcium antagonist, verapamil, on collateral perfusion in the absence of pharmacological tone. 2. Verapamil was the most potent vasodilator (EC50 = 72.6 +/- 32.0 nM) of 5-hydroxytryptamine/histamine-induced tone in the rabbit isolated perfused ear. Sodium nitroprusside and BRL 38227 were less potent with respective EC50 values of 488 +/- 75 nM and 296 +/- 40 nM. Following inhibition of endothelium-derived relaxing factor (EDRF) synthesis, the potency of BRL 38227 was significantly (P less than 0.001) increased with an EC50 of 55.6 +/- 5.0 nM. 3. BRL 38227 at 500 nM and 3 microM induced substantial increases in collateral perfusion following arterial ligation in the absence of pharmacological tone compared to control. Furthermore 3 microM BRL 38227 completely reversed the attenuation of collateral perfusion which followed inhibition of EDRF synthesis with 100 microM NG-nitro-L-arginine methyl ester (L-NAME). 4. Sodium nitroprusside (500 nM and 3 microM) induced modest improvements in collateral perfusion in the early stages after arterial occlusion. 5. Verapamil did not influence collateral perfusion at either of the concentrations used (50 nM and 3 microM), even though it was a potent vasodilator. 6. The results of this study indicate that BRL 38227, and to a much lesser extent sodium nitroprusside, selectively improve collateral perfusion following arterial occlusion, even in the presence of effects of EDRF on acute collateralization, while verapamil has no effect. Furthermore, BRL 38227 also improves collateral perfusion following inhibition of EDRF synthesis. It remains to be established whether BRL 38227 has beneficial actions in acute arterial occlusion in vivo.
authors.affiliation: Department of Diagnostic Radiology, University of Wales College of Medicine, Heath Park, Cardiff.
authors.forename: M D
authors.initials: MD
authors.lastname: Randall
authors.forename: T M
authors.initials: TM
authors.lastname: Griffith
mesh_terms: D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001157:Arterial Occlusive Diseases / Q000503:physiopathology; D001578:Benzopyrans / Q000494:pharmacology*; D019806:Cromakalim; D004431:Ear, External / Q000098:blood supply* / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology*; D011758:Pyrroles / Q000494:pharmacology*; D011817:Rabbits; D012039:Regional Blood Flow / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*; D014700:Verapamil / Q000494:pharmacology*
chemical_list: D001578:Benzopyrans; D011758:Pyrroles; D014665:Vasodilator Agents; D019806:Cromakalim; D009599:Nitroprusside; D009569:Nitric Oxide; D001120:Arginine; D014700:Verapamil; D019331:NG-Nitroarginine Methyl Ester