These studies will investigate the effects of post-natal age on pulmonary vascular reactivity, lung fluid balance, and endothelial modulation. Particular emphasis will be placed on the interactions with eicosanoids, as they are important for the normal transition of pulmonary hemodynamics which occurs at birth. Responses of the developing pulmonary circulation to eicosanoids will be evaluated at three ages: 0-4 days, 12-16 days, 2-3 months for lambs and .3 months (adults) for guinea pigs. The responses to be determined included magnitude and site of vascular reactivity to eicosanoids, their effects on neonatal lung fluid balance, and the potential interaction between age-related vascular reactivity to eicosanoids and modulation by the pulmonary vascular endothelium. The first specific aim of this proposal is to determine the site of pulmonary vascular responses to eicosanoids as a function of age in isolated perfused lamb lungs. These experiments will elucidate which vessels are most responsive to vasoactive eicosanoids, and how their reactivity is altered by development changes. The responses will be determined during normoxia and during hypoxia, as there is a significant interaction of 02 tension and pulmonary vascular tone an d/or reactivity. The second specific aim is to evaluate the effects of eicosanoids on lung fluid balance during this developmental period in isolated perfused lamb lungs. These studies will attempt to determine the contributions of hydrostatic pressures, vascular surface area, and vascular permeability with eicosanoid-induced pulmonary edema. The final specific aim will be to determine whether there is a difference in the modulation of pulmonary vascular reactivity by the endothelium due to developmental changes. Using isolated intra-pulmonary vessels from guinea pigs, the first goal os to determine the responses to classic endothelium-dependent and -independent compounds as a function of age. The second of this specific aim will be to determine the interaction of the endothelium with eicosanoids.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
First Independent Research Support & Transition (FIRST) Awards (R29)
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Human Embryology and Development Subcommittee 1 (HED)
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University of Maryland Baltimore
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Yuan, X J; Tod, M L; Rubin, L J et al. (1994) Deoxyglucose and reduced glutathione mimic effects of hypoxia on K+ and Ca2+ conductances in pulmonary artery cells. Am J Physiol 267:L52-63
Yuan, X J; Goldman, W F; Tod, M L et al. (1993) Hypoxia reduces potassium currents in cultured rat pulmonary but not mesenteric arterial myocytes. Am J Physiol 264:L116-23
Yuan, X J; Goldman, W F; Tod, M L et al. (1993) Ionic currents in rat pulmonary and mesenteric arterial myocytes in primary culture and subculture. Am J Physiol 264:L107-15
Tseng, C M; Goodman, L W; Rubin, L J et al. (1993) NG-monomethyl-L-arginine paradoxically relaxes preconstricted canine intrapulmonary arteries. J Appl Physiol 74:549-58
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Anderson, D E; Yuan, X J; Tseng, C M et al. (1993) Nitrone spin-traps block calcium channels and induce pulmonary artery relaxation independent of free radicals. Biochem Biophys Res Commun 193:878-85
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Tod, M L; Cassin, S (1992) Endothelin-1-induced pulmonary arterial dilation is reduced by N omega-nitro-L-arginine in fetal lambs. J Appl Physiol 72:1730-4