AJP - Lung Cellular and Molecular Physiology, Vol 273, Issue 1 275-L281, Copyright © 1997 by American Physiological Society

ARTICLES

Differential nitric oxide production by microvascular and macrovascular endothelial cells

M. Geiger, A. Stone, S. N. Mason, K. T. Oldham and K. S. Guice
Division of General Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA.

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 (approximately 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.

This article has been cited by other articles:

				R. Chang, L. G. Chicoine, H. Cui, N. L. Kanagy, B. R. Walker, Y. Liu, B. K. English, and L. D. Nelin Cytokine-induced arginase activity in pulmonary endothelial cells is dependent on Src family tyrosine kinase activity Am J Physiol Lung Cell Mol Physiol, October 1, 2008; 295(4): L688 - L697. [Abstract] [Full Text] [PDF]

				V. Hadkar, S. Sangsree, S. M. Vogel, V. Brovkovych, and R. A. Skidgel Carboxypeptidase-mediated enhancement of nitric oxide production in rat lungs and microvascular endothelial cells Am J Physiol Lung Cell Mol Physiol, July 1, 2004; 287(1): L35 - L45. [Abstract] [Full Text] [PDF]

				D. D. Bannerman and S. E. Goldblum Mechanisms of bacterial lipopolysaccharide-induced endothelial apoptosis Am J Physiol Lung Cell Mol Physiol, June 1, 2003; 284(6): L899 - L914. [Abstract] [Full Text] [PDF]

				R. A. Skidgel, X.-p. Gao, V. Brovkovych, A. Rahman, D. Jho, S. Predescu, T. J. Standiford, and A. B. Malik Nitric Oxide Stimulates Macrophage Inflammatory Protein-2 Expression in Sepsis J. Immunol., August 15, 2002; 169(4): 2093 - 2101. [Abstract] [Full Text] [PDF]

				B. R. Pitt and C. M. St. Croix Complex Regulation of iNOS in Lung Am. J. Respir. Cell Mol. Biol., January 1, 2002; 26(1): 6 - 9. [Full Text] [PDF]

				M. A. Vander Heyden, T. R. Halla, J. A. Madden, and J. B. Gordon Multiple Ca2+-dependent modulators mediate alkalosis-induced vasodilation in newborn piglet lungs Am J Physiol Lung Cell Mol Physiol, March 1, 2001; 280(3): L519 - L526. [Abstract] [Full Text] [PDF]

				T. R. Halla, J. A. Madden, and J. B. Gordon Mediators of alkalosis-induced relaxation of piglet pulmonary veins Am J Physiol Lung Cell Mol Physiol, May 1, 2000; 278(5): L968 - L973. [Abstract] [Full Text] [PDF]

				E. J. Pulido, B. D. Shames, D. A. Fullerton, B. C. Sheridan, C. H. Selzman, F. Gamboni-Robertson, D. D. Bensard, and R. C. McIntyre Jr Differential inducible nitric oxide synthase expression in systemic and pulmonary vessels after endotoxin Am J Physiol Regulatory Integrative Comp Physiol, May 1, 2000; 278(5): R1232 - R1239. [Abstract] [Full Text] [PDF]

				B. A. Johnson, B. R. Pitt, and P. Davies Pulmonary arterial smooth muscle cells modulate cytokine- and LPS-induced cytotoxicity in endothelial cells Am J Physiol Lung Cell Mol Physiol, March 1, 2000; 278(3): L460 - L468. [Abstract] [Full Text] [PDF]