Defibrotide modulates prostaglandin production in the rat mesenteric vascular bed.
Defibrotide 1 microM, a polydeoxyribonucleotide extracted from mammalian organs, reduced the contractile responses to noradrenaline (NA) in the rat isolated and perfused mesenteric vascular bed, in intact as well as in de-endothelialized preparations. Defibrotide was without effect on the acetylcholine-induced relaxations of U-46619-precontracted mesenteric vascular beds. Moreover, defibrotide increased 6-keto prostaglandin (PG) F(2alpha) (stable metabolite of prostacyclin) release sixfold in the presence, but not in the absence of the endothelium, with no modification on the release of other prostanoids. Defibrotide also inhibited the NA-induced increase in PGF(2alpha) release, in both intact and de-endothelialized mesenteric vascular beds. In conclusion, the present results show that defibrotide modulates PG production in the mesenteric bed and that the observed inhibition of the contractile responses should be due to the impairment of the NA-induced increase in PGF(2alpha) release.
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Instituto de Investigaciones Farmacológicas, CONICET, 1113, Buenos Aires, Argentina. usugurudu@yahoo.com.ar
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D015237:Dinoprost / Q000378:metabolism; D004336:Drug Antagonism; D004730:Endothelium, Vascular / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D011089:Polydeoxyribonucleotides / Q000494:pharmacology*; D011453:Prostaglandins / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D013152:Splanchnic Circulation / Q000187:drug effects*; D014661:Vasoconstriction / Q000187:drug effects
C078129:6-keto-prostaglandin F2alpha; D011089:Polydeoxyribonucleotides; D011453:Prostaglandins; C036901:defibrotide; D015237:Dinoprost; D000109:Acetylcholine; D009638:Norepinephrine