Effects of mast cell membrane stabilizing agents in a rat lung ischemia-reperfusion model.

Abstract

BACKGROUND:

The aim of this study was to test the hypothesis that agents which stabilize the mast cell membrane may modulate the phenotype of the vascular wall in a lung ischemia-reperfusion model, including altering expression of endothelial and leukocyte adhesion receptors and the inducible nitric oxide synthase (NOS-2).

METHODS:

Three sets of rats were given either intravenous saline (group A), ketotifen (group B), or cromolyn (group C), respectively. The left pulmonary artery was ligated temporarily and reopened after 2 hours of ischemia. Then, after a 2-hour period of reperfusion, the left lung was excised. ICAM-1 and NOS-2 were measured at the protein level by Western blotting, and cGMP levels were measured by enzyme-linked immunosorbent assay in the lung tissue specimens for each drug group.

RESULTS:

ICAM-1 expressions, determined as the intensity of a given band on the Western blot, were 197+/-59 in group B and 195+/-83 in group C versus 369+/-114 in group A (p = 0.002 for analysis of variance). In contrast with ICAM-1, NOS-2 expression was increased by ketotifen or cromolyn treatment (464+/-82 in group B and 507+/-93 in group C, compared with 377+/-44 for group A, p = 0.007). The finding of increased NOS-2 expression in groups B and C is consistent with the observed increase in tissue cGMP levels in the same groups (1.92+/-0.9 pmol/mL for group A versus 7.8+/-3.5 pmol/mL for group B, and 12.4+/-5.8 pmol/mL for group C, p = 0.0004).

CONCLUSIONS:

These data establish that mast cell stabilizing agents modulate the vascular phenotype in the setting of pulmonary ischemia and reperfusion by decreasing ICAM-1 expression, augmenting expression of NOS-2, and increasing tissue cGMP levels. As decreasing ICAM-1 expression and increasing cGMP levels have proven useful to limit proinflammatory mechanisms of tissue injury, mast cell stabilizing agents may provide a new therapeutic option to improve organ function in the setting of reperfusion.

• Authors: K M Vural, H Liao, M C Oz, D J Pinsky
• Journal: The Annals of thoracic surgery (Ann Thorac Surg) Vol. 69 Issue 1 Pg. 228-32 (Jan 2000) ISSN: 0003-4975 [Print] Netherlands
• PMID: 10654519 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Anti-Asthmatic Agents
• Histamine H1 Antagonists
• Intercellular Adhesion Molecule-1
• Nitric Oxide Synthase
• Cyclic GMP
• Cromolyn Sodium
• Ketotifen

Topics

• Analysis of Variance
• Animals
• Anti-Asthmatic Agents (therapeutic use)
• Cell Membrane (drug effects, metabolism)
• Cromolyn Sodium (therapeutic use)
• Cyclic GMP (analysis)
• Disease Models, Animal
• Endothelium, Vascular (drug effects, pathology)
• Histamine H1 Antagonists (therapeutic use)
• Intercellular Adhesion Molecule-1 (analysis, drug effects)
• Ischemia (metabolism, pathology)
• Ketotifen (therapeutic use)
• Lung (blood supply, pathology)
• Male
• Mast Cells (drug effects, metabolism)
• Nitric Oxide Synthase (analysis, drug effects)
• Phenotype
• Rats
• Rats, Sprague-Dawley
• Reperfusion Injury (metabolism, pathology, prevention & control)