Levels of endothelin-1 in embryos from control and neonatal streptozotocin-induced diabetic rats, and their relationship with nitric oxide generation.
Endothelin-1 (ET-1), a potent vasoconstrictor peptide and modulator of vasoactive substances such as prostanoids and nitric oxide (NO), plays an important role during embryo and fetal development. In this work, ET-1, nitrate and nitrite, and prostaglandin E2 (PGE2) levels in embryos from control and neonatal streptozotocin-induced (n-stz) diabetic rats were assessed, and the modulatory pathways regulating the generation of these vasoactive agents investigated. Endothelin-1 concentrations were found to be increased in embryos from n-stz diabetic rats when compared with controls. Additions of spermine NONOate, a nitric oxide donor, enhanced ET-1 levels in embryos from both control and n-stz diabetic rats, whereas N(G)-monomethyl-L-arginine, a nitric oxide inhibitor, diminished embryonic ET-1 content. Thus, enhanced ET-1 levels in the embryos from n-stz diabetic rats may be related to the elevated NO levels found in those embryos. Additions of ET-1 or bosentan (an endothelin A and endothelin B receptor antagonist), did not alter PGE2 generation in embryos from either control or n-stz diabetic rats. Endothelin-1 additions diminished nitrate and nitrite levels in embryos from both control and n-stz diabetic rats, whereas bosentan stimulated nitrate and nitrite generation in those embryos. In the present work, it was found that ET-1 levels were enhanced in embryos from n-stz diabetic rats, probably as a result of NO overproduction, an alteration which may be related to embryonic abnormalities and growth delay. Endothelin-1 has been shown to be a negative modulator of embryonic NO levels, a mechanism likely to be important during development. Endothelin-1 may prevent damage induced by NO overproduction in embryos from n-stz diabetic rats.
Sinner
Debora
D
Centro de Estudios Farmacologicos y Botánicos, Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina.
Jawerbaum
Alicia
A
Pustovrh
Carolina
C
White
Verónica
V
Capobianco
Evangelina
E
Gonzalez
Elida
E
D000015:Abnormalities, Multiple / Q000209:etiology; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D016022:Case-Control Studies; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism; D004622:Embryo, Mammalian / Q000187:drug effects / Q000378:metabolism*; D019332:Endothelin-1 / Q000378:metabolism*; D005260:Female; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009573:Nitrites / Q000378:metabolism; D011247:Pregnancy; D011254:Pregnancy in Diabetics; D011506:Proteins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013096:Spermine / Q000494:pharmacology; D013311:Streptozocin; D019323:omega-N-Methylarginine / Q000494:pharmacology
D019332:Endothelin-1; D009566:Nitrates; D020030:Nitric Oxide Donors; D009573:Nitrites; D011506:Proteins; D019323:omega-N-Methylarginine; D013096:Spermine; D009569:Nitric Oxide; D013311:Streptozocin; D015232:Dinoprostone