Exhaled NO and plasma cGMP increase after endotoxin infusion in healthy volunteers

Abstract

Nitric oxide (NO) is believed to be involved in the pathophysiology of sepsis. This study evaluated the activity of the NO pathway in a human endotoxin model.At baseline and after endotoxin, on-line measurements of exhaled NO (eNO) were made using a chemiluminescence technique with a single-breath method. NO-free air was inhaled prior to exhalation against a resistance. NO in orally and nasally exhaled air and in rectal gas was investigated. Plasma nitrite, nitrate, and guanosine 39, 59-monophosphate (cGMP) and the events after diclophenac administration were also studied.Endotoxin infusion resulted in tachycardia and fever. An early increase in oral eNO concentration was observed and oral eNO decreased after diclophenac administration. NO exhaled nasally, NO in rectum gas and nitrite/nitrate levels remained unchanged over the study period. cGMP increased after 4 h.These findings suggest an early increase in nitric oxide production from the lungs, probably due to increased activity of the constitutive nitric oxide synthase upon endotoxin stimulation. In contrast, nitric oxide production in the upper airways, measured as nasally exhaled nitric oxide and nitric oxide in rectal gas, remained unchanged. Further studies will elucidate if exhaled nitric oxide is a valuable marker of sepsis-induced lung injury and if monitoring of treatment is possible. Eur Respir J 2003; 21: 594-599.

Enrichment of lung microbiome with supraglottic taxa is associated with increased pulmonary inflammation

“…The association between specific pneumotype and airway inflammation was evaluated utilizing eNO based on prior observations describing increased eNO in pulmonary infections and following lipopolysaccharide administration [45-47]. Our results extend these observations by demonstrating that elevated eNO may occur in association with a specific pneumotype even in the absence of overt pneumonia.…”

Nicotinamide does not influence cytokines or exhaled NO in human experimental endotoxaemia

“…In contradiction to dose-response studies in vitro [24,25], we found no effect on the inflammatory parameters by nicotinamide. In agreement with our previous studies, the endotoxin challenge evoked a marked increase in temperature, cytokines and exhaled NO [14,26]. We have previously reported data on endotoxin effect on human volunteers regarding plasma nitrite/nitrate, cGMP, platelet and leucocyte activation [14,26,27].…”

“…In agreement with our previous studies, the endotoxin challenge evoked a marked increase in temperature, cytokines and exhaled NO [14,26]. We have previously reported data on endotoxin effect on human volunteers regarding plasma nitrite/nitrate, cGMP, platelet and leucocyte activation [14,26,27]. Further, the human experimental setup with repetitive endotoxin provocations provided to be a consistent, reproducible and stable model for randomised studies.…”

Adenosine infusion attenuates soluble RAGE in endotoxin‐induced inflammation in human volunteers

“…Endotoxin (2 ng kg )1 ) elicited the expected clinical signs of an inflammatory reaction (tachycardia, fever), prominent release of cytokines studied, in agreement with previous findings in volunteers (Suffredini et al 1989, Soop et al 2003b. Endotoxin (2 ng kg )1 ) elicited the expected clinical signs of an inflammatory reaction (tachycardia, fever), prominent release of cytokines studied, in agreement with previous findings in volunteers (Suffredini et al 1989, Soop et al 2003b.…”