Role of the endothelium and nitric oxide synthases in modulating superoxide formation induced by endotoxin and cytokines in porcine pulmonary arteries

Abstract

Background: The interactive roles of cytokines, endotoxins, superoxide (O 2 v -) and nitric oxide (NO) in the pathogenesis of adult respiratory distress syndrome (ARDS) have not been fully elucidated. The effects of tumour necrosis factor-α (TNF-α), interleukin 1α (IL-1α), and lipopolysaccharide (LPS) and the role of NO and the endothelium in mediating O 2 v -formation were therefore investigated in intact porcine pulmonary arteries in vitro. Methods: Intrapulmonary artery (PA) segments were obtained from White Landrace pigs (25-35 kg) and incubated with LPS, IL-1α, and TNF-α and O 2 v -release was measured by the superoxide dismutase (SOD) inhibitable reduction of ferricytochrome c. The source of O 2 v -formation was determined using a number of enzyme inhibitors. The role of NO was explored using NO synthase (NOS) inhibitors and the distribution of NOS isoforms and peroxynitrite (ONOO

Higher Urine Nitric Oxide Is Associated with Improved Outcomes in Patients with Acute Lung Injury

“…It is possible that NO or NOx are protective during ALI. NO scavenges oxygen free radicals that are generated during oxidative stress (4,33). NO vasodilates the microcirculation, which allows for increased perfusion of tissue beds (33).…”

Nitroaspirins and Morpholinosydnonimine but Not Aspirin Inhibit the Formation of Superoxide and the Expression of gp91 phox Induced by Endotoxin and Cytokines in Pig Pulmonary Artery Vascular Smooth Muscle Cells and Endothelial Cells

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“…5 In turn, TNF-␣ and ILs and lipopolysaccharide (LPS) upregulate enzymes that generate O 2 ·Ϫ in cultured vascular tissues, in particular, NADPH oxidase. 6,7 A selfperpetuating inflammatory cascade ensues.…”

Vein graft failure: current clinical practice and potential for gene therapeutics

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