Loren P. Thompson, Ph.D.
Laboratory of Fetal Cardiovascular Regulation
Oxygen deprivation to the fetus is one of the leading causes of fetal morbidity and mortality. In response to hypoxia, fetal cardiac output increases to high priority organs such as the heart, brain, and adrenal glands and decreases to low priority organs such as skeletal muscle, gut and skin. The vascular mechanisms responsible for altering organ perfusion during fetal hypoxia are poorly understood. Our laboratory studies the effects of fetal hypoxia and gestational age on endothelial and vascular smooth muscle function of the fetal circulation. We have shown a maturational increase in nitric oxide-mediated relaxation of fetal renal arteries and expression of endothelium-specific nitric oxide synthase mRNA of the fetal renal cortex. We have also shown that differences in oxygen sensitivity exist among fetal arteries. We are investigating the effect of prolonged hypoxia on gene expression of endothelium-derived substances of the fetal vasculature and how this alters vascular smooth muscle function. We use Northern blot, ribonuclease protection assay, enzyme activity assays, and reverse transcription-polymerase chain reaction (RT-PCR) for determining hypoxic and gestational effects on gene expression. We measure biomechanical activity of isolated fetal arteries for determining functional responses. Thus, molecular, biochemical and physiological approaches are used to test the hypothesis that decreased oxygenation alters the gene expression of the fetal vascular endothelium and modulates the vascular tone to specific organ beds. These experiments will identify the important contribution of endothelium-derived vasoactive substances such as nitric oxide during prolonged hypoxia and how altered synthesis is responsible for changes in vascular reactivity in the fetal circulation. This experimental approach will provide needed information on how the fetal vasculature adapts to short and long term oxygen deprivation and how vascular reactivity is altered during fetal hypoxia.
Recent Publications:Thompson LP, Weiner CP 1996 Acetylcholine relaxation of renal artery and nitric oxide synthase activity of renal cortex increase with fetal and postnatal age. Pediatr Res 40:192-197.
Weiner CP, Thompson LP, VanVoorhis B 1995 The role of nitric oxide in female reproduction. Fetal and Maternal Medicine Review 7:175-205.
Thompson LP, Weiner CP 1995 Oxygen sensitivity of NO-mediated relaxation differs between fetal guinea pig arteries. Endothelium 3:88.
Thompson LP, Weiner CP 1993 Endothelium-derived relaxing factor inhibits norepinephrine contraction of fetal guinea pig arteries. Am J Physiol 264 (Heart Circulatory Physiology 33):H1139-H1145.
