We propose to test the following hypothesis. (1) local release of PGI2 NO contributes to the relaxation of umbilical and fetoplacental vascular smooth muscle. (2) A dimunition in the formation of these endothelial derived vasodilators under increase 02 tension promotes contraction of umbilical and fetoplacental vascular smooth muscle. (3) Reduced formation of endothelial derived vasodilators modulates the sensitivity of fetoplacental vessels to endogenous vasoconstrictor substances and may contribute to the increase in placental resistance which is thought to occur in some diseased states.
Three specific aims are proposed to achieve our objective and each aim corresponds to a part of the hypothesis. (1) To study the release and actions of PGI2 and NO on human umbilical and fetoplacental vessels obtained from normal pregnancies. (2) To study the interrelationship of PGI2 and NO release and action on human umbilical and fetoplacental vessels under different 01 tensions. (3) To study the release and action of PGI2 and NO on umbilical and fetoplacental vessels obtained from some abnormal pregnancies and evaluate whether these substances modulate the actions of angiotension II and serotonin. Long term objectives. The generation and actions of EDRF and PGI2 and their interrelationship may have important basic and clinical implications. The results of these studies may indicate whether diminished formation or actin of these substances may contribute to the closure of the umbilical artery immediately after birth and form the basis for future studies. The results would also lay the basis for future studies to assess the role of PGI2 and EDRF in the pathophysiology of certain abnormal pregnancies where the fetoplacental circulation is adversely affected.
