The Research Plan is aimed at the basic biology relating to the most important cause of neonatal morbidity and mortality: preterm delivery. Without completely understanding the initiation of parturition, efforts to reduce preterm delivery have been and will be hampered. Dr. Sladek proposes to test the hypothesis that nitric oxide is an endogenous regulator of uterine contractility which promotes quiescence during pregnancy. Dr. Sladek's preliminary studies of late pregnancy rabbits demonstrate that nitric oxide synthase (NOS) activity is present in the decidua; that uterine NOS activity has the characteristics of the inducible isoform of the enzyme; and that uterine NOS activity decreases 80% on the last day of pregnancy.
The Specific aims are: 1) to extend uterine NOS activity studies to non pregnant, early and mid pregnancy, and post partum rabbits; 2) to localize uterine NOS on the tissue, cellular, and subcellular level; 3) to determine whether uterine NOS is a unique isoform of the enzyme; and 4) to determine the physiologic contribution of nitric oxide to uterine quiescence. The research design is a two pronged approach of biochemical and whole animal physiology experiments.
| Sladek, S M; Westerhausen-Larson, A; Roberts, J M (1999) Endogenous nitric oxide suppresses rat myometrial connexin 43 gap junction protein expression during pregnancy. Biol Reprod 61:8-13 |
| Sladek, S M; Kanbour-Shakir, A; Watkins, S et al. (1998) Granulated metrial gland cells contain nitric oxide synthases during pregnancy in the rat. Placenta 19:55-65 |
| Sladek, S M; Magness, R R; Conrad, K P (1997) Nitric oxide and pregnancy. Am J Physiol 272:R441-63 |
