M Bernareggi, JA Mitchell, PJ Barnes and MG Belvisi
National Heart and Lung Institute, Imperial College of Science, Technology and Medicine, London, United Kingdom.

In the rat, plasma leakage in various vascular beds, including the whole lung, occurs after administration of lipopolysaccharide (LPS). LPS-induced microvascular plasma leakage in many organs is associated with an enhanced formation of nitric oxide (NO) after the induction of nitric oxide synthase (iNOS). However, there is limited information concerning the relationship between NO and plasma leakage into the airways. LPS (10 mg/kg, intravenously) caused a significant leakage of Evans blue dye, a marker of microvascular permeability, at 240 min in the trachea which was inhibited by the NOS inhibitor, NG-nitro-L- arginine methyl ester (L-NAME; 10 mg/kg, intravenously), or dexamethasone (1 mg/kg, intravenously). This effect was paralleled by an increase in calcium-independent iNOS activity, assessed by measuring the conversion of radiolabeled L-arginine to L-citrulline, in LPS- treated animals. In contrast, L-NAME significantly increased plasma leakage in the trachea of vehicle-treated rats and this effect was inhibited by indomethacin. These results suggest that under "physiological" conditions endogenous NO suppresses plasma leakage but when iNOS is expressed the increased production of NO enhances plasma leakage. These findings may implicate a role for NO in the maintenance of airway function and in the inflammatory process occurring in diseases such as asthma, where iNOS is known to be expressed.

This article has been cited by other articles:

				R Ratnawati and P S Thomas Exhaled nitric oxide in paediatric asthma Chronic Respiratory Disease, July 1, 2005; 2(3): 163 - 174. [Abstract] [PDF]

				F. L. M. Ricciardolo, P. J. Sterk, B. Gaston, and G. Folkerts Nitric Oxide in Health and Disease of the Respiratory System Physiol Rev, July 1, 2004; 84(3): 731 - 765. [Abstract] [Full Text] [PDF]

				M. A. Birrell, K. McCluskie, E.-B. Haddad, C. H. Battram, S. E. Webber, M. L. Foster, M. H. Yacoub, and M. G. Belvisi Pharmacological Assessment of the Nitric-Oxide Synthase Isoform Involved in Eosinophilic Inflammation in a Rat Model of Sephadex-Induced Airway Inflammation J. Pharmacol. Exp. Ther., March 1, 2003; 304(3): 1285 - 1291. [Abstract] [Full Text] [PDF]

				L. F. Wang, M. Patel, H. M. Razavi, S. Weicker, M. G. Joseph, D. G. McCormack, and S. Mehta Role of Inducible Nitric Oxide Synthase in Pulmonary Microvascular Protein Leak in Murine Sepsis Am. J. Respir. Crit. Care Med., June 15, 2002; 165(12): 1634 - 1639. [Abstract] [Full Text] [PDF]

				N. Marczin and D. Royston Editorial I: Nitric oxide as mediator, marker and modulator of microvascular damage in ARDS Br. J. Anaesth., August 1, 2001; 87(2): 179 - 183. [Full Text] [PDF]

				T. KOBAYASHI, E. C. GABAZZA, S. SHIMIZU, H. YASUI, H. YUDA, O. HATAJI, K. MARUYAMA, T. YAMAUCHI, K. SUZUKI, Y. ADACHI, et al. Long-term Inhalation of High-dose Nitric Oxide Increases Intraalveolar Activation of Coagulation System in Mice Am. J. Respir. Crit. Care Med., June 1, 2001; 163(7): 1676 - 1682. [Abstract] [Full Text] [PDF]

				A. L. Mundy and K. L. Dorrington Inhibition of nitric oxide synthesis augments pulmonary oedema in isolated perfused rabbit lung Br. J. Anaesth., October 1, 2000; 85(4): 570 - 576. [Abstract] [Full Text] [PDF]

				K. ARSALANE, F. BROECKAERT, B. KNOOPS, M. WIEDIG, G. TOUBEAU, and A. BERNARD Clara Cell Specific Protein (CC16) Expression after Acute Lung Inflammation Induced by Intratracheal Lipopolysaccharide Administration Am. J. Respir. Crit. Care Med., May 1, 2000; 161(5): 1624 - 1630. [Abstract] [Full Text]

				P. J. BARNES Endogenous Inhibitory Mechanisms in Asthma Am. J. Respir. Crit. Care Med., March 1, 2000; 161(3): S176 - 181. [Full Text] [PDF]

				P. J. Barnes, K. F. Chung, and C. P. Page Inflammatory Mediators of Asthma: An Update Pharmacol. Rev., December 1, 1998; 50(4): 515 - 596. [Abstract] [Full Text] [PDF]

				S. Mehta, J. Boudreau, C. M. Lilly, and J. M. Drazen Endogenous pulmonary nitric oxide in the regulation of airway microvascular leak Am J Physiol Lung Cell Mol Physiol, November 1, 1998; 275(5): L961 - L968. [Abstract] [Full Text] [PDF]

				H. Takano, H.-B. Lim, Y. Miyabara, T. Ichinose, T. Yoshikawa, and M. Sagai Oral Administration of L-Arginine Potentiates Allergen-Induced Airway Inflammation and Expression of Interleukin-5 in Mice J. Pharmacol. Exp. Ther., August 1, 1998; 286(2): 767 - 771. [Abstract] [Full Text]

				R. A. Robbins, P. A. Jinkins, T. W. Bryan, S. C. Prado, and S. A. Milligan Methotrexate Inhibition of Inducible Nitric Oxide Synthase in Murine Lung Epithelial Cells In Vitro Am. J. Respir. Cell Mol. Biol., June 1, 1998; 18(6): 853 - 859. [Abstract] [Full Text]

				M. A Sapienza, S. A Kharitonov, I. Horvath, K F. Chung, and P. J Barnes Effect of inhaled L-arginine on exhaled nitric oxide in normal and asthmatic subjects Thorax, March 1, 1998; 53(3): 172 - 175. [Abstract] [Full Text]

				X.-P. Gao, S. R. Akhter, and I. Rubinstein Ovalbumin increases macromolecular efflux from the in situ nasal mucosa of allergic hamsters J Appl Physiol, January 1, 1998; 84(1): 169 - 176. [Abstract] [Full Text] [PDF]

				A. J. Gow, S. R. Thom, and H. Ischiropoulos Nitric oxide and peroxynitrite-mediated pulmonary cell death Am J Physiol Lung Cell Mol Physiol, January 1, 1998; 274(1): L112 - L118. [Abstract] [Full Text] [PDF]

				X.-P. Gao Tannic acid elicits neurogenic plasma exudation from the in situ hamster cheek pouch Am J Physiol Regulatory Integrative Comp Physiol, January 1, 1998; 274(1): R237 - R242. [Abstract] [Full Text] [PDF]

				J. G. Filep, A. Delalandre, and M. Beauchamp Dual Role for Nitric Oxide in the Regulation of Plasma Volume and Albumin Escape During Endotoxin Shock in Conscious Rats Circ. Res., November 19, 1997; 81(5): 840 - 847. [Abstract] [Full Text]

				H. INOUE, H. AIZAWA, K. MATSUMOTO, M. SHIGYO, S. TAKATA, M. HARA, and N. HARA Effect of beta 2-agonists on Histamine-induced Airway Microvascular Leakage in Ozone-exposed Guinea Pigs Am. J. Respir. Crit. Care Med., September 1, 1997; 156(3): 723 - 727. [Abstract] [Full Text] [PDF]