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 hemorheologic agent in the treatment of peripheral vascular disease. In rings precontracted with phenylephrine (0.1 microM), pentoxifylline (10 nM-10 microM) induced concentration-dependent relaxations which were not modified after incubation with indomethacin (3 microM) but which were almost completely abolished after incubation with methylene blue (10 microM) or after mechanical removal of the endothelium. After incubation with pentoxifylline (10 microM) 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.
Berkenboom
G
G
Department of Cardiology, Erasmus Hospital, Brussels, Belgium.
Fang
Z Y
ZY
Unger
P
P
Goldman
M
M
Fontaine
J
J
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D005576:Colforsin / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000502:physiology*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009569:Nitric Oxide / Q000494:pharmacology; D010431:Pentoxifylline / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000494:pharmacology
D005576:Colforsin; D009569:Nitric Oxide; D012701:Serotonin; D000109:Acetylcholine; D010431:Pentoxifylline; D008751:Methylene Blue; D007213:Indomethacin