Levels of endothelin-1 in embryos from control and neonatal-streptozotocin diabetic rats, and their relationship with nitric oxide generation

SINNER DÉBORA; JAWERBAUM ALICIA; PUSTOVRH CAROLINA; WHITE VERÓNICA; CAPOBIANCO EVANGELINA; GONZÁLEZ ELIDA

REPRODUCTION FERTILITY AND DEVELOPMENT

CSIRO PUBLISHING

Lugar: Peth, Australia; Año: 2002 vol. 14 p. 23 - 28

1031-3613

Endothelin-1 (ET-1), a potent vasoconstrictor peptide and modulator of vasoactive substances such us prostanoids and nitric oxide (NO), plays an important role during embryo and fetal development. In this work, we assessed ET-1, nitrate and nitrite and prostaglandin E2 (PGE2) levels in embryos from control and neonatal streptozotocin induced (n-stz) diabetic rats, and we investigated the modulatory pathways regulating the generation of these vasoactive agents. ET-1 concentrations were found to be increased in the embryos from n-stz diabetic rats when related to controls. Additions of spermine NONOate, a nitric oxide donor, enhance ET-1 levels in both embryos from control and n-stz diabetic rats, whereas NG-monomethyl-L-arginine (L-NMMA), 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 (ETA) and endothelin B (ETB) receptor antagonist), did not alter PGE2 generation in embryos from both control and n-stz diabetic rats. ET-1 additions diminished nitrate and nitrite levels in embryos from both control and n-stz diabetic rats, whereas bosentan stimulates nitrate and nitrite generation in those embryos. In the present work, we found that ET-1 levels are enhanced in the embryos from n-stz diabetic rats, probably as a result of NO overproduction, an alteration that may be related to embryonic abnormalities and growth delay. ET-1 has been shown to be a negative modulator of embryonic NO levels, a mechanism likely to be important during development. ET-1 may prevent damage induced by NO overproduction in the embryos from n-stz diabetic rats.