ENDOTHELIUM-DEPENDENT EFFECTS OF PENTOXIFYLLINE IN RAT AORTA

Experiments were performed with isolated rat aortas to study the vasoactive properties of pentoxifylline, a cyclic AMP phosphodiesterase inhibitor, which is used as a haemorrheologic agent in the treatment of peripheral vascular disease. In rings precontracted with phenylephrine (0.1-mu-M), pentoxifylline (10 nM-10-mu-M) induced concentration-dependent relaxations which were not modified after incubation with indomethacin (3-mu-M) but which were almost completely abolished after incubation with methylene blue (10-mu-M) or after mechanical removal of the endothelium. After incubation with pentoxifylline (10-mu-M) for 30 min, the concentration-response curves for endothelium-dependent relaxations to acetylcholine were shifted to the left and the serotonin-induced contractions were decreased, while the relaxations to forskolin, which are endothelium-independent and cyclic AMP-mediated, were not altered. We conclude that pentoxifylline exerts vasoactive effects that are mediated by endothelium-derived relaxing factor (EDRF), and that pentoxifylline has negligible endothelium-independent vasodilating properties. These properties of inducing or potentiating EDRF-mediated effects might contribute to the efficacy of pentoxifylline in the treatment of vascular disease.