This Article Full Text Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Filep, J. G. Articles by Beauchamp, M. Search for Related Content PubMed PubMed Citation Articles by Filep, J. G. Articles by Beauchamp, M.

(Circulation Research. 1997;81:840-847.)
© 1997 American Heart Association, Inc.

Articles

Dual Role for Nitric Oxide in the Regulation of Plasma Volume and Albumin Escape During Endotoxin Shock in Conscious Rats

János G. Filep, Aline Delalandre, , Micheline Beauchamp

From the Research Center, Maisonneuve-Rosemont Hospital, Department of Medicine, University of Montréal, Québec, Canada.

Correspondence to János G. Filep, MD, Research Center, Maisonneuve-Rosemont Hospital, Department of Medicine, University of Montréal, 5415 boulevard de l'Assomption, Montréal, Québec, Canada H1T 2M4.

Abstract To assess the role of nitric oxide (NO) produced by the constitutive (cNOS) and inducible NO synthase (iNOS) in the regulation of vascular functions, we compared the effects of aminoguanidine, a relatively selective inhibitor of iNOS, and N^G-nitro-L-arginine methyl ester (L-NAME), a nonselective NOS inhibitor on blood pressure, plasma volume, and albumin escape during the early and delayed phases of endotoxin shock in conscious, chronically catheterized rats. Red blood cell volume and plasma volume were determined by using chromium-51–tagged erythrocytes and iodine-125–labeled albumin, respectively. Injection of lipopolysaccharide (LPS) 10 mg/kg IV resulted in a fall in blood pressure, hemoconcentration, and increased total-body albumin escape, which is reflected by a 25% reduction in plasma volume. When LPS was injected into animals pretreated with L-NAME (7.4 µmol/kg IV 15 minutes before LPS), losses in plasma volume and albumin escape were significantly greater than in rats that received LPS alone, despite that L-NAME attenuated the hypotensive action of LPS. Aminoguanidine pretreatment (162 µmol/kg) had no effect on the early responses to LPS, whereas it was as potent as L-NAME in reversing hypotension when injected 70 minutes after LPS. Aminoguanidine treatment also prevented further losses in plasma volume and markedly attenuated total-body and organ albumin escape rates elicited by LPS. L-NAME produced only a slight attenuation of LPS-induced losses in plasma volume and albumin escape in most organs studied, whereas it potentiated albumin extravasation in the lung. These results demonstrate that inhibition of cNOS potentiates, whereas inhibition of iNOS markedly attenuates, losses in plasma volume and albumin escape elicited by LPS, and suggest that selective inhibitors of iNOS may be more effective than nonselective inhibitors of all forms of NOS in the therapy of septic shock.

Key Words: aminoguanidine • N^G-nitro-L-arginine methyl ester • vascular permeability • septic shock • nitric oxide

This article has been cited by other articles:

				D. El Kebir, L. Jozsef, W. Pan, and J. G. Filep Myeloperoxidase Delays Neutrophil Apoptosis Through CD11b/CD18 Integrins and Prolongs Inflammation Circ. Res., August 15, 2008; 103(4): 352 - 359. [Abstract] [Full Text] [PDF]

				M. D. Lehner, D. Marx, R. Boer, A. Strub, C. Hesslinger, M. Eltze, W.-R. Ulrich, F. Schwoebel, R. T. Schermuly, and J. Barsig In Vivo Characterization of the Novel Imidazopyridine BYK191023 [2-[2-(4-Methoxy-pyridin-2-yl)-ethyl]-3H-imidazo[4,5-b]pyridine], a Potent and Highly Selective Inhibitor of Inducible Nitric-Oxide Synthase J. Pharmacol. Exp. Ther., April 1, 2006; 317(1): 181 - 187. [Abstract] [Full Text] [PDF]

				D. Predescu, S. Predescu, J. Shimizu, K. Miyawaki-Shimizu, and A. B. Malik Constitutive eNOS-derived nitric oxide is a determinant of endothelial junctional integrity Am J Physiol Lung Cell Mol Physiol, September 1, 2005; 289(3): L371 - L381. [Abstract] [Full Text] [PDF]

				T. Kovesi, D. Royston, M. Yacoub, and N. Marczin Basal and nitroglycerin-induced exhaled nitric oxide before and after cardiac surgery with cardiopulmonary bypass Br. J. Anaesth., May 1, 2003; 90(5): 608 - 616. [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]

				V. Mooser, M. M. Berger, L. Tappy, C. Cayeux, S. M. Marcovina, R. Darioli, P. Nicod, and R. Chiolero Major Reduction in Plasma Lp(a) Levels During Sepsis and Burns Arterioscler Thromb Vasc Biol, April 1, 2000; 20(4): 1137 - 1142. [Abstract] [Full Text] [PDF]

				P. Andrew, Y. Deng, and S. Kaufman Fluid extravasation from spleen reduces blood volume in endotoxemia Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2000; 278(1): R60 - R65. [Abstract] [Full Text] [PDF]