The present study is designed to evaluate the mechanism(s) responsible for increased systemic arterial pressure, reduced uteroplacental blood flow and proteinuria which occurs in response to maternal hypocalcemia in late term pregnant sheep. Pregnancy-induced hypertension (PIH) in women is known to be associated with similar changes in these parameters. The onset of PIH occurs in pregnant women when the maternal and fetal calcium demands are at their maximum. Additionally, recent studies have shown that reduction in calcium levels leads to a significant decrease in prostacyclin synthesis in vascular smooth muscle which has also been observed in PIH. The present proposal is designed to evaluate the maternal and fetal cardiovascular response to maternal hypocalcemia and to utilize this model to understand the underlying pathophysiology of PIH. Studies are planned which will evaluate systemic and uterine vascular responses to hypocalcemia and determine if changes occur in uterine and umbilical vascular resistance and reactivity in hypocalcemic animals. In these studies the effects of hypocalcemia and the resultant hypertension in fetal and placental growth will also be determined. Furthermore, we plan to carefully evaluate umbilical and uterine changes which occur with internal and external doppler ultrasound wave profiles (S/D ratios, pulsatility indices) response to maternal hypertension as well as in response to exogenously administered vasoconstrictors. Changes in systolic and diastolic velocity ratios will be determined and compared using both implanted doppler flow probes on the uterine and umbilical circulation and external continuous wave spectral analysis doppler equipment. These values will be related to fetal PaO2,O2 content, pH and lactate. Studies will also evaluate local uterine and umbilical responses to vasoconstrictors and determine if prostacyclin (PGI2, measured as 6 oxo PGF 1alpha) release in response to these vasoconstrictors is altered in hypertensive animals compared to controls. These studies will provide us with new and exciting information regarding this model of PIH.
