(Circulation. 1997;95:553-554.)
© 1997 American Heart Association, Inc.
Articles |
Nitric Oxide: Nature's Naturally Occurring Leukocyte Inhibitor
Jefferson Medical Center, Thomas Jefferson University, Philadelphia, Pa.
Correspondence to Allan M. Lefer, PhD, Department of Physiology, Jefferson Medical College, Thomas Jefferson University, 1020 Locust St, Philadelphia, PA 19107.
Key Words: Editorials • atherosclerosis • endothelium • endothelium-derived factors • leukocytes
 |
Introduction |
|---|
The vascular endothelium produces NO, which is basally released at concentrations of about 2 to 20 nmol/L.1 2 This NO diffuses to the subjacent vascular smooth muscle, where it regulates vascular tone.3 4 However, the endothelially derived NO also diffuses to the luminal surface of the endothelium, where it exerts a number of important physiological effects, including (1) scavenging of superoxide radicals,5 6 (2) inhibition of platelet adherence and aggregation,7 8 (3) modulation of endothelial layer permeability,9 and (4) attenuation of leukocyte function.10 11 This antileukocyte effect of NO has several components. First, NO markedly attenuates leukocyte rolling along the endothelium by inhibiting the expression of P-selectin on the vascular endothelium.11 12 Second, NO inhibits the firm adherence of leukocytes to the endothelium,11 12 13 partially by inhibition of ICAM-1 and VCAM-1 expression.14 Downregulation of these cell adhesion molecules by NO occurs through inhibition of protein kinase C activation15 and via prevention of the transcription factor nuclear factor-
B, which usually induces expression of the mRNA for these adhesion molecules.14 Third, NO inhibits leukocyte action by inhibiting the cytoassembly of NADPH oxidase,16 thereby attenuating the release of superoxide radicals by activated leukocytes, particularly granulocytes.17 These effects of NO pertain to both neutrophils and monocytes and appear to be relevant to atherosclerosis.
Against this backdrop of important effects of physiological concentrations of NO, effective NO levels are decreased in a variety of circulatory disorders, including myocardial ischemia-reperfusion,18 19 20 circulatory shock and trauma,21 22 and hypercholesterolemia and atherosclerosis.23 24 The decrease in NO levels occurs in the early stages of hypercholesterolemia before the
This article has been cited by other articles:
 |
|
 |
|
  A. Alipour, A. J.H. H.M van Oostrom, A. Izraeljan, C. Verseyden, J. M. Collins, K. N. Frayn, T. W.M. Plokker, J. W. F. Elte, and M. Castro Cabezas Leukocyte Activation by Triglyceride-Rich Lipoproteins Arterioscler Thromb Vasc Biol, April 1, 2008; 28(4): 792 - 797. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Fatini, L. Mannini, E. Sticchi, E. Cecchi, A. Bruschettini, E. Leprini, P. Pagnini, G. F. Gensini, D. Prisco, and R. Abbate eNOS Gene Affects Red Cell Deformability: Role of T-786C, G894T, and 4a/4b Polymorphisms Clinical and Applied Thrombosis/Hemostasis, October 1, 2005; 11(4): 481 - 488. [Abstract] [PDF]
|
|
|
|
 |
|
 C. Fatini, F. Sofi, A. M. Gori, E. Sticchi, R. Marcucci, M. Lenti, A. Casini, C. Surrenti, R. Abbate, and G. F. Gensini Endothelial Nitric Oxide Synthase -786T>C, but Not 894G>T and 4a4b, Polymorphism Influences Plasma Homocysteine Concentrations in Persons with Normal Vitamin Status Clin. Chem., July 1, 2005; 51(7): 1159 - 1164. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J U Kim, H K Chang, S S Lee, J W Kim, K T Kim, S W Lee, and W T Chung Endothelial nitric oxide synthase gene polymorphisms in Behcet's disease and rheumatic diseases with vasculitis Ann Rheum Dis, November 1, 2003; 62(11): 1083 - 1087. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. van Haperen, M. de Waard, E. van Deel, B. Mees, M. Kutryk, T. van Aken, J. Hamming, F. Grosveld, D. J. Duncker, and R. de Crom Reduction of Blood Pressure, Plasma Cholesterol, and Atherosclerosis by Elevated Endothelial Nitric Oxide J. Biol. Chem., December 6, 2002; 277(50): 48803 - 48807. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Ogawa, K. Shikata, M. Matsuda, S. Okada, H. Usui, J. Wada, N. Taniguchi, and H. Makino Protective effect of a novel and selective inhibitor of inducible nitric oxide synthase on experimental crescentic glomerulonephritis in WKY rats Nephrol. Dial. Transplant., December 1, 2002; 17(12): 2117 - 2121. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Honjo, H. Tanihara, K. Nishijima, J. Kiryu, Y. Honda, B. Y. J. T. Yue, and T. Sawamura Statin Inhibits Leukocyte-Endothelial Interaction and Prevents Neuronal Death Induced by Ischemia-Reperfusion Injury in the Rat Retina Arch Ophthalmol, December 1, 2002; 120(12): 1707 - 1713. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.Y. Jeremy, G.D. Angelini, M. Khan, D.P. Mikhailidis, R.J. Morgan, C.S. Thompson, K.R. Bruckdorfer, and K.M. Naseem Platelets, oxidant stress and erectile dysfunction: an hypothesis Cardiovasc Res, April 1, 2000; 46(1): 50 - 54. [Full Text] [PDF]
|
|
|
|
|
|
J. Y. Jeremy, D. Rowe, A. M. Emsley, and A. C. Newby Nitric oxide and the proliferation of vascular smooth muscle cells Cardiovasc Res, August 15, 1999; 43(3): 580 - 594. [Full Text] [PDF]
|
|
|
|
|
|
H. Tomita, K. Egashira, M. Kubo-Inoue, M. Usui, M. Koyanagi, H. Shimokawa, M. Takeya, T. Yoshimura, and A. Takeshita Inhibition of NO Synthesis Induces Inflammatory Changes and Monocyte Chemoattractant Protein-1 Expression in Rat Hearts and Vessels Arterioscler Thromb Vasc Biol, September 1, 1998; 18(9): 1456 - 1464. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. S. Ali, M. Gandhi, B. A. Finegan, A. Koshal, and A. S. Clanachan Cardioprotection by Activation of NO/cGMP Pathway After Cardioplegic Arrest and 8-Hour Storage Ann. Thorac. Surg., May 1, 1998; 65(5): 1303 - 1309. [Abstract] [Full Text] [PDF]
|
|