Differential nitric oxide production by microvascular and macrovascular endothelial cells

被引:46
作者
Geiger, M
Stone, A
Mason, SN
Oldham, KT
Guice, KS
机构
[1] DUKE UNIV, MED CTR, DIV GEN SURG, DEPT SURG, DURHAM, NC 27710 USA
[2] DUKE UNIV, MED CTR, DIV PEDIAT SURG, DEPT SURG, DURHAM, NC 27710 USA
关键词
lung injury; rat; pulmonary microvasculature;
D O I
10.1152/ajplung.1997.273.1.L275
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
Phenotypic heterogeneity among endothelial cell populations may account for important organ-specific behaviors. Experimental evidence suggests that endothelium-derived nitric oxide mediates certain of these unique responses. The purpose of these investigations was to compare rat pulmonary microvascular endothelial cells with pulmonary artery and aortic macrovascular endothelial cells in their ability to generate nitric oxide (NO). Cultures of these microvascular and macrovascular endothelial cells were incubated with interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), and Salmonella typhimurium lipopolysaccharide (LPS) alone or in combination, and nitrite production was measured. Single-agent exposure with IFN-gamma (up to 1,000 U/ml), TNF-alpha (up to 60,000 U/ml), or LPS (up to 500 ng/ml) had little effect on nitrite generation. Nitrite production by rat aortic macrovascular endothelial cells (RAEC) was significantly greater than that by the rat lung microvascular endothelial cells (RLMVEC) when stimulated with TNF-alpha + IFN-gamma, LPS + IFN-gamma, or TNF-alpha + LPS. The maximal response by all endothelial cell types (similar to 15-fold increase in RAEC and 8-fold increase in RLMVEC) was observed with LPS + IFN-gamma. The nitrite generation from rat pulmonary artery endothelial cells was intermediate between RAEC and RLMVEC responses when stimulated with IFN-gamma + LPS or TNF-alpha. Similar patterns of heterogeneous inducible nitric oxide synthase mRNA induction occurred when Northern analysis of specimens from the cultured endothelial cell types was done. These data suggest that phenotypic heterogeneity between these endothelial cell populations is substantial and, by inference, that site-specific NO . generation may occur.
引用
收藏
页码:L275 / L281
页数:7
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