JOURNAL HOME CME HOME THIS MONTH PAST ISSUES ETOC COLLECTIONS AUTHORS REVIEWERS EDITORIAL BOARD FEEDBACK RSS HELP
		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Fischer, L. G. Articles by Sielenkämper, A. W. Search for Related Content PubMed PubMed Citation Articles by Fischer, L. G. Articles by Sielenkämper, A. W. Related Collections Resuscitation Critical Care Trauma

---

CRITICAL CARE AND TRAUMA

Bradykinin-Induced Pulmonary Vasoconstriction Is Time and Inducible Nitric Oxide Synthase Dependent in a Peritonitis Sepsis Model

Department of Anesthesiology and Intensive Care, University of Münster, Münster, Germany

Address correspondence and reprint requests to Lars G. Fischer, MD, University of Münster, Department of Anesthesiology and Intensive Care, 48149 Münster, Germany. Address e-mail to fischer-l{at}anit.uni-muenster.de

In an isolated perfused lung model, bradykinin induced pulmonary vasoconstriction in rats made septic by the injection of lipopolysaccharide (LPS). To mimic the pathophysiology of sepsis in humans more closely, we investigated pulmonary endothelial injury in a peritonitis model (cecal ligation and perforation; CLP). Male Sprague-Dawley rats were randomly divided into nine groups (n = 6–8). LPS and CLP rats were compared after 6 h with and without treatment with a selective inhibitor of inducible nitric oxide synthase (iNOS), L-N₆-(1-iminoethyl)-lysine. Time dependency was investigated in CLP-treated rats at 24 h. The pulmonary circulation was isolated and perfused with a constant flow after the rats’ tracheas were intubated and ventilated. Bradykinin (1, 3, and 6 µg) was injected, and changes in perfusion pressure were measured. Lungs were harvested for Western blot analysis to determine the role of iNOS in pulmonary endothelial dysfunction. In contrast to CLP 24 h rats, dose-dependent bradykinin-induced pulmonary vasoconstriction was observed in LPS and CLP 6 h rats. Concomitant administration of L-N₆-(1-iminoethyl)-lysine significantly attenuated this vasoconstriction in both groups. The iNOS protein was expressed in lung homogenates from LPS 6 h and CLP 6 h but not from CLP 24 h rats. Both sepsis models caused bradykinin-induced pulmonary vasoconstriction, with the CLP groups demonstrating a time dependency of this effect. In conjunction with the time-dependent decrease in iNOS protein, the attenuated bradykinin-induced vasoconstriction due to selective iNOS inhibition suggests an important role for iNOS in pulmonary endothelial injury for both sepsis models.

IMPLICATIONS: This study demonstrated in a more clinical sepsis model (cecal ligation and perforation) a time dependency of bradykinin-induced vasoconstriction in an isolated perfused rat lung setup, indicating endothelial injury. Inducible nitric oxide synthase appeared to play an important role in the pathogenesis of this pulmonary endothelial dysfunction.

This article has been cited by other articles:

				S. Lauer, H. Freise, L. G. Fischer, K. Singbartl, H. V. Aken, M. M. Lerch, and A. W. Sielenkamper The Role of Thoracic Epidural Analgesia in Receptor-Dependent and Receptor-Independent Pulmonary Vasoconstriction in Experimental Pancreatitis Anesth. Analg., August 1, 2007; 105(2): 453 - 459. [Abstract] [Full Text] [PDF]

Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999