Effects of nitrovasodilators on the human fetal-placental circulation in vitro.
This study examines the vasorelaxation of isolated human placental chorionic plate arteries and the perfused fetal-placental vasculature, in vitro, to a variety of nitrovasodilator compounds including glyceryl trinitrate (GTN) sodium nitroprusside (SNP), S-nitroso-N-acetylpenicillamine (SNAP), S-nitroso-N-glutathione (SNG) and NaNO(2). The effects of these compounds were also examined under conditions of high (>450 mmHg) and low oxygen (<50 mmHg) tension. In a separate series of experiments the effects of GTN and NaNO(2)were further investigated with addition of the antioxidants cysteine (100 microm), glutathione (100 microm) or superoxide dismutase (SOD) (30 I.U./ml). The order of nitrovasodilator potency, when added directly to isolated fetal vessels was GTN=SNP>SNAP=SNG>NaNO(2). The order under low oxygen tension was similar, GTN=SNP>SNG= SNAP>or=NaNO(2). SNG ( approximately fourfold) and NaNO(2)( approximately 50-fold) were significantly more potent under low oxygen conditions. Cysteine, glutathione and SOD were without effect on GTN induced vasodilatation. However, all three agents significantly enhanced (six- to ninefold) the effects of NaNO(2)under similar conditions. When infused directly into the fetal-placental circulation during in vitro perfusion experiments the order of potency was GTN>SNP>or=SNG>or=SNAP>or=NaNO(2). When the nitrovasodilators were infused indirectly via the maternal intervillous space the order of potency was GTN>or=SNP>or=NaNO(2)>or=SNAP=SNG. Our observations suggest that there are important differences in the action of different classes of nitrovasodilator compounds on the fetal-placental circulation. The changes observed with SNG and NaNO(2)may be influenced by levels of tissue oxygenation.
Zhang
X Q
XQ
Department of Obstetrics and Gynaecology, The 3rd Affiliated Hospital, Sun Yat-Sen University of Medical Sciences, China.
Kwek
K
K
Read
M A
MA
Donoghue
J F
JF
Walters
W A
WA
D000293:Adolescent; D000328:Adult; D000975:Antioxidants / Q000494:pharmacology; D001158:Arteries / Q000502:physiology; D002823:Chorion / Q000098:blood supply; D003545:Cysteine / Q000494:pharmacology; D005260:Female; D005333:Fetus / Q000098:blood supply*; D005865:Gestational Age; D005978:Glutathione / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D009566:Nitrates / Q000494:pharmacology; D005996:Nitroglycerin / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D009603:Nitroso Compounds / Q000494:pharmacology; D010100:Oxygen / Q000008:administration & dosage; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D010920:Placenta / Q000098:blood supply*; D011247:Pregnancy; D026422:S-Nitrosoglutathione; D013482:Superoxide Dismutase / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
D000975:Antioxidants; D009566:Nitrates; D009603:Nitroso Compounds; C110881:S-nitro-N-acetylpenicillamine; D014665:Vasodilator Agents; D009599:Nitroprusside; D026422:S-Nitrosoglutathione; C031618:sodium nitrate; D013482:Superoxide Dismutase; D005996:Nitroglycerin; D005978:Glutathione; D010396:Penicillamine; D003545:Cysteine; D010100:Oxygen