EFFECTS OF POLYSORBATES AND CREMOPHOR EL ON VASCULAR-RESPONSES IN RATAORTA

The effects of Tween 20, Tween 80, and Cremophor EL, surface active ag ents which are used for dispersion of water-insoluble substances, on v ascular responsiveness were investigated using rat aortic rings. In hi gh concentrations all these agents produced persistent contractions in aortic rings independent of the presence of endothelium. These contra ctions were not influenced by inhibitors of known endogenous contracti le mediators. Incubation with these agents caused a concentration-depe ndent inhibition of the endothelium-dependent relaxant responses to ac etylcholine in intact precontracted aortic rings. Endothelium-independ ent relaxations produced by sodium nitroprusside were not inhibited, b ut rather potentiated in the presence of Tween 80 (10(-1) ml/l). On th e other hand, Tween 80 inhibited the contractile effects of 5-hydroxyt ryptamine, phenylephrine, and bradykinin significantly. The data sugge sts that these substances affect both endothelial cells and vascular s mooth muscle.