Temporal determination of lung NO system and COX-2 upregulation following ischemia-reperfusion injury.

Abstract:

BACKGROUND:Pulmonary ischemia-reperfusion (IR) is a biopathological event detectable in several clinical conditions, including lung transplantation, cardiopulmonary bypass, resuscitation, and pulmonary embolism. The understanding behind the activation of various inflammatory mediators regulating the apoptotic pathways remains largely unknown. We investigated the temporal expression of endothelial nitric oxide (eNOS), inducible (iNOS), and cyclooxygenase-2 (COX-2) proteins following lung-IR injury. METHODS:Lung IR was induced in anesthetized rats. One hour ischemia was performed by clamping the left hilum. eNOS, iNOS, and COX-2 levels in the bronchoalveolar lavage (BAL) were measured at different time points after restoring lung perfusion in conjunction with histological changes and cellular apoptosis. RESULTS:BAL-eNOS levels were increased as early as 3 hours post IR, attaining the highest values (5.5 U/mL) at 3 hours, compared to non-IR values (2.8 U/mL). BAL-iNOS increased at 3-hour post-IR (3 U/mL). iNOS reached the highest levels at 24 hours (4.5 U/mL) as compared to nonischemic lungs (1.8 U/mL). COX-2 peaked at 12 hours (.025 U/mL) compared to 3, 24, and 48 hours. Highest apoptotic rates were detected at 12 and 48 hours following IR. CONCLUSIONS:The time-associated involvement of eNOS, iNOS, and COX-2 enzymes during the evolution of IR injury may point to an early reaction of the NOSs system versus the COX-2. Similar patterns of enzymatic activity were previously shown in the context of lung IR injury. This temporal activation may indicate an involvement of eNOS in an early reparative response, and possibly the late-pathological response, mediated by the coinduction of iNOS-COX-2.

journal_name

Exp Lung Res

authors

Dolkart O,E A,S S,S M,P G,Aa W

doi

10.3109/01902148.2013.858196

subject

Has Abstract

pub_date

2014-02-01 00:00:00

pages

22-9

issue

1

eissn

0190-2148

issn

1521-0499

journal_volume

40

pub_type

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