Endothelium-dependent effects of pentoxifylline in rat aorta. 1991

G Berkenboom, and Z Y Fang, and P Unger, and M Goldman, and J Fontaine
Department of Cardiology, Erasmus Hospital, Brussels, Belgium.

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.

UI MeSH Term Description Entries
D007213 Indomethacin A non-steroidal anti-inflammatory agent (NSAID) that inhibits CYCLOOXYGENASE, which is necessary for the formation of PROSTAGLANDINS and other AUTACOIDS. It also inhibits the motility of POLYMORPHONUCLEAR LEUKOCYTES. Amuno,Indocid,Indocin,Indomet 140,Indometacin,Indomethacin Hydrochloride,Metindol,Osmosin
D008297 Male Males
D008751 Methylene Blue A compound consisting of dark green crystals or crystalline powder, having a bronze-like luster. Solutions in water or alcohol have a deep blue color. Methylene blue is used as a bacteriologic stain and as an indicator. It inhibits GUANYLATE CYCLASE, and has been used to treat cyanide poisoning and to lower levels of METHEMOGLOBIN. Methylthionine Chloride,Swiss Blue,Basic Blue 9,Chromosmon,Methylene Blue N,Methylthioninium Chloride,Urolene Blue,Blue 9, Basic,Blue N, Methylene,Blue, Methylene,Blue, Swiss,Blue, Urolene
D009119 Muscle Contraction A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments. Inotropism,Muscular Contraction,Contraction, Muscle,Contraction, Muscular,Contractions, Muscle,Contractions, Muscular,Inotropisms,Muscle Contractions,Muscular Contractions
D009126 Muscle Relaxation That phase of a muscle twitch during which a muscle returns to a resting position. Muscle Relaxations,Relaxation, Muscle,Relaxations, Muscle
D009131 Muscle, Smooth, Vascular The nonstriated involuntary muscle tissue of blood vessels. Vascular Smooth Muscle,Muscle, Vascular Smooth,Muscles, Vascular Smooth,Smooth Muscle, Vascular,Smooth Muscles, Vascular,Vascular Smooth Muscles
D009569 Nitric Oxide A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP. Endogenous Nitrate Vasodilator,Mononitrogen Monoxide,Nitric Oxide, Endothelium-Derived,Nitrogen Monoxide,Endothelium-Derived Nitric Oxide,Monoxide, Mononitrogen,Monoxide, Nitrogen,Nitrate Vasodilator, Endogenous,Nitric Oxide, Endothelium Derived,Oxide, Nitric,Vasodilator, Endogenous Nitrate
D010431 Pentoxifylline A METHYLXANTHINE derivative that inhibits phosphodiesterase and affects blood rheology. It improves blood flow by increasing erythrocyte and leukocyte flexibility. It also inhibits platelet aggregation. Pentoxifylline modulates immunologic activity by stimulating cytokine production. Agapurin,BL-191,Oxpentifylline,Pentoxil,Torental,Trental,BL 191,BL191
D011919 Rats, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding. August Rats,Inbred Rat Strains,Inbred Strain of Rat,Inbred Strain of Rats,Inbred Strains of Rats,Rat, Inbred Strain,August Rat,Inbred Rat Strain,Inbred Strain Rat,Inbred Strain Rats,Inbred Strains Rat,Inbred Strains Rats,Rat Inbred Strain,Rat Inbred Strains,Rat Strain, Inbred,Rat Strains, Inbred,Rat, August,Rat, Inbred Strains,Rats Inbred Strain,Rats Inbred Strains,Rats, August,Rats, Inbred Strain,Strain Rat, Inbred,Strain Rats, Inbred,Strain, Inbred Rat,Strains, Inbred Rat
D004730 Endothelium, Vascular Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components. Capillary Endothelium,Vascular Endothelium,Capillary Endotheliums,Endothelium, Capillary,Endotheliums, Capillary,Endotheliums, Vascular,Vascular Endotheliums

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