The hypothesis is that ET-1 is a critically important regulator of placental perfusion, and thus fetal growth and pregnancy outcome. The investigator will evaluate the molecular mechanisms regulating the activities of both ET-1 and NO in uteroplacental perfusion and IUGR. The investigator will also evaluate the role of endogenous ET-1 in the pathophysiology of IUGR using an ET-1 receptor antagonist.
Aim 1 is to evaluate the role of ET-1 in the pathophysiology of IUGR.
Aim 2 is to investigate the molecular mechanisms regulating ET-1 and NO in the pathophysiology of IUGR.
In Aim 1, the investigator will evaluate the effects of an ETA on fetal and placental weight (Exp 1), uteroplacental blood flow measured with radioactive microspheres (Exp 2), maternal hypertension and proteinuria (Exp 3), and placental necrosis (Exp 4) of rats treated with a NOS inhibitor.
In Aim 2, the expression of ET-1 peptide, ET-1 mRNA, ETA and ETB receptor mRNA and binding sites, endothelin converting enzyme, and NOS activity and protein mass will be measured in rats exposed to hypoxia and to NOS inhibition. Cellular localization of ET, ET receptors, and NOS isoforms will be performed with immunocytochemistry.
