Defibrotide normalizes cardiovascular function hampered by established atherosclerosis in the rabbit.
In a previous paper we gave evidence that chronic oral defibrotide antagonizes the noxious effect of developing atherosclerosis in the cardiovascular system. In the present paper we give evidence that defibrotide is still capable of exerting beneficial effects on cardiovascular function once atherosclerosis is established. In fact, there was statistically significant amelioration by defibrotide infusion in the following, all of which were hampered by established atherosclerosis: in rabbit aorta relaxation to acetylcholine, prostaglandin E2, and 6-keto-prostaglandin F1alpha generation from rabbit aortas, rabbit heart left ventricular end-diastolic pressure, coronary perfusion pressure, and left ventricular developed pressure, vasopressor activity of acetylcholine and endothelin-1 on coronary perfusion pressure, and 6-keto-prostaglandin F1alpha generation from the rabbit heart. Since prostacyclin takes part in NO generation, is cellular protective, and inhibits 5-lipoxygenase product synthesis, its increase, caused by defibrotide, could explain defibrotide cardioprotective activity. Prostacyclin activity could be backed by prostaglandin E2, another cardioprotective prostaglandin.
Rossoni
G
G
Department of Pharmacology, Chemotherapy and Medical Toxicology, University of Milan, Italy. giuseppe.rossoni@unimi.it
Berti
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Trento
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Cattaneo
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Porta
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Pescador
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Ferro
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D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000737:chemistry / Q000502:physiology; D001161:Arteriosclerosis / Q000188:drug therapy* / Q000503:physiopathology; D001794:Blood Pressure; D001835:Body Weight / Q000187:drug effects; D002320:Cardiovascular Physiological Phenomena / Q000187:drug effects*; D002791:Cholesterol, Dietary / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism; D019332:Endothelin-1 / Q000187:drug effects / Q000378:metabolism; D005343:Fibrinolytic Agents / Q000627:therapeutic use; D006321:Heart / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D008055:Lipids / Q000097:blood; D008297:Male; D009119:Muscle Contraction; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D009929:Organ Size / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D011089:Polydeoxyribonucleotides / Q000627:therapeutic use*; D011817:Rabbits; D015424:Reperfusion; D016277:Ventricular Function, Left / Q000187:drug effects
D002791:Cholesterol, Dietary; D019332:Endothelin-1; D005343:Fibrinolytic Agents; D008055:Lipids; D010975:Platelet Aggregation Inhibitors; D011089:Polydeoxyribonucleotides; C036901:defibrotide; D015121:6-Ketoprostaglandin F1 alpha; D015232:Dinoprostone; D000109:Acetylcholine