Placental dysfunction in Suramin-treated rats--a new model for pre-eclampsia.
Impaired placentation and oxidative stress are proposed to play major roles in the pathogenesis of placental dysfunction and pre-eclampsia. This study was carried out to evaluate if inhibited angiogenesis by Suramin injections in early pregnancy may cause a condition resembling pre-eclampsia in rats. Rats of two different Sprague-Dawley strains, U and H, were given intraperitoneal injections of Suramin or saline in early pregnancy. The outcome of pregnancy was evaluated on gestational day 20. Suramin injections caused increased blood pressure and decreased renal blood flow in the U rats. In both rat strains Suramin decreased the placental blood flow and caused fetal growth retardation. In both strains the placental concentration of the isoprostane 8-epi-PGF2alpha was increased, indicating oxidative stress. The serum concentration of Endothelin-1 was increased in the U rats. The U strain had a lower basal placental blood flow, and the effects of Suramin were more pronounced in this strain. We conclude, that Suramin injections to pregnant rats cause a state of placental insufficiency, which partly resembles human pre-eclampsia. The induction of this condition is at least partly mediated by oxidative stress, and is subject to varied genetic susceptibility.
Nash
P
P
Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden.
Wentzel
P
P
Lindeberg
S
S
Naessén
T
T
Jansson
L
L
Olovsson
M
M
Eriksson
U J
UJ
D020533:Angiogenesis Inhibitors / Q000633:toxicity*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D004573:Electrolytes / Q000097:blood; D019332:Endothelin-1 / Q000097:blood; D005260:Female; D006801:Humans; D028421:Isoprostanes / Q000378:metabolism; D008055:Lipids / Q000097:blood; D009573:Nitrites / Q000097:blood; D010920:Placenta / Q000098:blood supply / Q000187:drug effects* / Q000503:physiopathology*; D011225:Pre-Eclampsia / Q000209:etiology* / Q000503:physiopathology*; D011247:Pregnancy; D011256:Pregnancy Outcome; D011507:Proteinuria / Q000209:etiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D012079:Renal Circulation / Q000187:drug effects; D013498:Suramin / Q000633:toxicity*; D015430:Weight Gain / Q000187:drug effects
D020533:Angiogenesis Inhibitors; D004573:Electrolytes; D019332:Endothelin-1; D028421:Isoprostanes; D008055:Lipids; D009573:Nitrites; D013498:Suramin