Neurotensin pulmonary metabolism in normal and asthmatic subjects

Eur Rev Med Pharmacol Sci. May-Jun 2003;7(3):75-80.

Abstract

Background: The role of pulmonary metabolism of endogenous neurotensin (NT) in asthma is still unclear. Information on this subject in humans is scarce.

Objectives: Evaluation of the pulmonary metabolism of the endogenous NT in asthmatic subjects during symptom-free periods and after a methacoline challenge test and in healthy individuals.

Methods: Ten asthmatic subjects (aged 34 to 70 years), diagnosed with extrinsic (n = 5), atopic (n = 3), and mixed asthma (n = 2), were compared to a group of 10 healthy individuals (aged 45 to 69 years). The asthmatic group of patients was evaluated with a PD20-FEV1 methacoline challenge test 3 days after a washout period from cessation of their regular medications. Two catheters were inserted in order to draw blood samples for the evaluation of NT concentration: one was inserted into the pulmonary artery and the other into the radial artery. The mean concentration of NT in pulmonary and systemic arterial blood, as well as the arteriovenous difference of NT and the absolute value of production rate [PR/m'], PR/m'/kg and PR/m'/m2 were calculated for each participant.

Results: The mean neurotensin concentration in normal subjects was higher in mixed venous blood (pulmonary artery) than in systemic arterial blood (p < 0001). Similarly, mean NT mixed venous levels in asthmatic subjects was shown to be higher than mean NT levels in systemic arterial blood, before and after the bronchoconstriction with methacoline (p = 0.05 and p = 0.02, respectively). In contrast, the arterovenous difference and the mean values of PR of NT were similar in both groups.

Conclusions: Our findings suggest that (1) NT concentration in mixed venous blood changes in transit through the pulmonary parenchyma, indicating that the pulmonary parenchyma is an important site of NT metabolism; (2) Pulmonary clearance of NT is unaffected by cholinergic bronchoconstriction. Further clinical studies are needed in order to improve both the understanding and the therapeutic approach of the neurogenic process in asthmatic subjects.

Publication types

  • Clinical Trial
  • Comparative Study
  • Controlled Clinical Trial

MeSH terms

  • Adult
  • Aged
  • Asthma / chemically induced*
  • Asthma / metabolism*
  • Humans
  • Lung / metabolism*
  • Male
  • Methacholine Chloride / administration & dosage
  • Methacholine Chloride / adverse effects*
  • Middle Aged
  • Neurotensin / metabolism*

Substances

  • Methacholine Chloride
  • Neurotensin