OXYGEN MODULATION OF FETAL VASCULAR ENDOTHELIUM

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Obstetric complications resulting in reduced uteroplacental perfusion greatly increase fetal mortality. Under these circumstances, fetal vascular adjustments are required to maintain adequate perfusion of organs critical for the normal growth and development of the fetus. The fetus responds to hypoxemia by redistributing cardiac output to organs such as the heart, brain, and adrenal gland The vascular mechanisms underlying this redistribution are poorly understood. In the adult circulation, the endothelium modulates vascular tone by release of vasoactive substances and is influenced by changes in oxygen tension. We hypothesize that fetal endothelium modulates vascular tone by releasing vasoactive autacoids in response to changes in oxygen tension. We further hypothesize that, in vivo, the fetal endothelium is an important oxygen sensing site and influences vascular reactivity to circulating hormones via oxygen-sensitive mechanisms. The effect of changes in oxygen tension on endothelium-dependent relaxation and agonist-induced contraction will be measured in isolated carotid and pulmonary arteries from guinea pig fetuses from 0.5 to near term gestation. Further, the vascular responses of isolated perfused mesenteric preparations will be measured to study reactivity of resistance-sized arteries. The response of the endothelium to changes in oxygen will be investigated in arteries from newborn and adult guinea pigs to characterize the adaptive changes in the endothelium after birth. SPECIFIC AIMS: 1) To determine the effect of gestational age on endothelium-dependent mechanisms in fetal arteries. 2) To determine the effect of oxygen on endothelium-dependent modulation of contraction and relaxation of isolated fetal arteries. 3) To determine the effect of maturation on oxygen sensitivity of the endothelium between fetal, newborn, and adult arteries.