Elevated levels of endothelin-1 and prostaglandin E2 and their effect on nitric oxide generation in placental tissue from neonatal streptozotocin-induced diabetic rats.
Endothelin-1 (ET-1), nitric oxide (NO) and prostaglandin E(2) (PGE(2)) are regulators of feto-placental hemodynamics. In this study we explore the inter-regulatory pathways that modulate the levels of these vasoactive agents in control and neonatal streptozotocin-induced (n-stz) diabetic rat placenta. ET-1 levels are increased in diabetic placenta when compared to controls (P<0.001), and are strongly reduced by an NO synthase inhibitor (P<0.001). PGE(2) production is increased in diabetic placenta when compared to controls (P<0.01), but these levels are not modulated by ET-1. NO levels, similar in control and in diabetic placenta, are not influenced by PGE(2), but they are negatively modulated by ET-1 in both control (P<0.05) and diabetic (P<0.01) placenta. We conclude that rat placental ET-1 inhibits NO levels but does not modify PGE(2) concentrations. The elevated levels of ET-1 and PGE(2) in diabetic placenta, potent vasoconstrictors of placental vasculature, are probably related to the induction of placental insufficiency and fetal hypoxia in this pathology.
Capobianco
E
E
Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Centro de Estudios Farmacológicos y Botánicos (CEFYBO), Serrano 669, Buenos Aires 1414, Argentina.
Jawerbaum
A
A
White
V
V
Pustovrh
C
C
Sinner
D
D
Gonzalez
E T
ET
D000818:Animals; D000831:Animals, Newborn; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000503:physiopathology; D015232:Dinoprostone / Q000378:metabolism*; D019332:Endothelin-1 / Q000378:metabolism*; D005260:Female; D005311:Fetal Hypoxia / Q000209:etiology / Q000503:physiopathology; D009569:Nitric Oxide / Q000096:biosynthesis*; D010920:Placenta / Q000098:blood supply / Q000378:metabolism*; D010927:Placental Insufficiency / Q000209:etiology / Q000503:physiopathology; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D014661:Vasoconstriction / Q000502:physiology
D019332:Endothelin-1; D009569:Nitric Oxide; D015232:Dinoprostone