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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
1R01HL040872-01A1
Application #
3358153
Study Section
Human Embryology and Development Subcommittee 2 (HED)
Project Start
1989-08-01
Project End
1992-07-31
Budget Start
1989-08-01
Budget End
1990-07-31
Support Year
1
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of California Los Angeles
Department
Type
Schools of Medicine
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Varela, A F; Runge, A; Ignarro, L J et al. (1992) Nitric oxide and prostacyclin inhibit fetal platelet aggregation: a response similar to that observed in adults. Am J Obstet Gynecol 167:1599-604
Hayashi, T; Fukuto, J M; Ignarro, L J et al. (1992) Basal release of nitric oxide from aortic rings is greater in female rabbits than in male rabbits: implications for atherosclerosis. Proc Natl Acad Sci U S A 89:11259-63
Vargas, H M; Cuevas, J M; Ignarro, L J et al. (1991) Comparison of the inhibitory potencies of N(G)-methyl-, N(G)-nitro- and N(G)-amino-L-arginine on EDRF function in the rat: evidence for continuous basal EDRF release. J Pharmacol Exp Ther 257:1208-15
Chaudhuri, G; Buga, G M; Gold, M E et al. (1991) Characterization and actions of human umbilical endothelium derived relaxing factor. Br J Pharmacol 102:331-6
Chaudhuri, G; Furuya, K (1991) Endothelium-derived vasoactive substances in fetal placental vessels. Semin Perinatol 15:63-7
Vargas, H M; Ignarro, L J; Chaudhuri, G (1990) Physiological release of nitric oxide is dependent on the level of vascular tone. Eur J Pharmacol 190:393-7