Collateral perfusion: the role of endothelium-derived relaxing factor and effects of vasodilators

An in vitro rabbit ear model has been used to investigate the role of endothelium-derived relaxing factor (EDRF) in collateral perfusion after acute arterial occlusion and also the effects of vasodilators. Collateral perfusion of an arterial segment isolated between occlusions was assessed by x-ray microangiography and was found to develop in a time-dependent manner. Inhibition of EDRF synthesis with NG-nitro-L-arginine methyl ester (L-NAME) greatly impaired collateral perfusion, indicating that the development of collateral perfusion was dependent on EDRF activity. This inhibitory effect was reversed by an excess of L-arginine. Further studies using vasodilators with different modes of action indicated that BRL 38227 (the active enantiomer of cromakalim, a potassium channel activator) substantially enhanced collateral perfusion, sodium nitroprusside had early beneficial effects, and verapamil had no effect.