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Effects of BRL 38227, sodium nitroprusside and verapamil on collateral perfusion following acute arterial occlusion in the rabbit isolated ear
Author(s) -
Randall Michael D.,
Griffith Tudor M.
Publication year - 1992
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1992.tb14334.x
Subject(s) - sodium nitroprusside , verapamil , pharmacology , perfusion , anesthesia , phentolamine , vasodilation , chemistry , medicine , cromakalim , endocrinology , nitric oxide , calcium , propranolol , agonist , receptor
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 (EC 50 = 72.6 ± 32.0 n m ) of 5‐hydroxytryptamine/histamine‐induced tone in the rabbit isolated perfused ear. Sodium nitroprusside and BRL 38227 were less potent with respective EC 50 values of 488 ± 75 n m and 296 ± 40 n m . Following inhibition of endothelium‐derived relaxing factor (EDRF) synthesis, the potency of BRL 38227 was significantly ( P < 0.001) increased with an EC 50 of 55.6 ± 5.0 n m . 3 BRL 38227 at 500 n m and 3 μ m induced substantial increases in collateral perfusion following arterial ligation in the absence of pharmacological tone compared to control. Furthermore 3 μ m BRL 38227 completely reversed the attenuation of collateral perfusion which followed inhibition of EDRF synthesis with 100 μ m N G ‐nitro‐ l ‐arginine methyl ester ( l ‐NAME). 4 Sodium nitroprusside (500 n m and 3 μ m ) 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 n m and 3 μ m ), 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 .