Are increased ATP blood levels responsible for PGI2 release from endothelium?
Defibrotide, a polydeoxyribonucleotide with profibrinolytic and antithrombotic properties obtained from mammalian lungs was shown capable of favoring the release of prostacyclin from endothelial cells. We previously evidenced that the use of defibrotide i.p. (32 mg/kg for 30 min) or orally (50 mg/kg for 1 h) induced a significant increase in 2,3-diphosphoglycerate (2,3-DPG) content of blood cells in rats. We tested the in-vivo capacity of defibrotide to modify over 90 min the blood content of ATP, cAMP and 2,3-DPG. Male Wistar rats were anaesthetized with pentobarbital (20 mg/kg) i.p.; the left carotid artery was cannulated with a polyethylene tube, from which 0.4 ml of blood was drawn at 0, 5, 10, 15, 20, 30, 40, 50, 60 and 90 min. At 0 min, defibrotide was administered i.p. or i.v. (through the femoral vein) at the dose of 1 ml containing 80 mg of drug or orally at the dose of 1 ml containing 160 mg of drug. The control rats employed received either the vehicle of the drug or physiologic saline. Our results demonstrated a significant drug-related increase with time (maximal levels were revealed about 20 min after i.v., i.p., or oral defibrotide treatment) of blood ATP content and a significant decrease in cAMP content as compared with the controls. Our data confirm the relation between increased drug-induced prostacyclin production and that of ATP of in blood.
Salari
P C
PC
Instituto di Patologia Generale, Università degli Studi di Milano, Italy.
Marni
A
A
Parisé
M
M
Calvani
A B
AB
Spaggiari
P G
PG
Gaja
G
G
Ferrero
M E
ME
D019794:2,3-Diphosphoglycerate; D000255:Adenosine Triphosphate / Q000097:blood*; D000818:Animals; D000242:Cyclic AMP / Q000097:blood; D004163:Diphosphoglyceric Acids / Q000097:blood; D004730:Endothelium, Vascular / Q000378:metabolism*; D011464:Epoprostenol / Q000378:metabolism*; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D008297:Male; D011089:Polydeoxyribonucleotides / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D004163:Diphosphoglyceric Acids; D005343:Fibrinolytic Agents; D011089:Polydeoxyribonucleotides; D019794:2,3-Diphosphoglycerate; C036901:defibrotide; D000255:Adenosine Triphosphate; D011464:Epoprostenol; D000242:Cyclic AMP