The Role of Endothelium-Derived Mediators in Exercise-Induced Bronchoconstriction

Abstract

Background: Exercise-induced bronchoconstriction (EIB) is a highly prevalent condition whose pathogenesis and effect on airways remain unclear. The aim of the study was to evaluate the changes in endothelial-derived mediators following intensive exercise in asthmatic patients. Methods: The study was conducted in a group of 25 asthmatic patients (15 with EIB, 10 without EIB) and 8 healthy volunteers. Changes induced by intensive exercise in the plasma concentrations of endothelin-1 (ET-1), thrombomodulin and soluble E-selectin were determined. Moreover, the possible correlations of these measurements with the results of baseline lung function, bronchial hyperreactivity (BHR), exhaled nitric oxide (F_ENO), baseline eosinophil cationic protein, peripheral blood eosinophilia and total IgE were investigated. Results: In the group of asthmatics with EIB, statistically significantly higher baseline concentrations of ET-1 and soluble E-selectin compared with asthmatics with negative exercise test results were revealed. In this group of patients, ET-1, thrombomodulin and soluble E-selectin concentrations significantly increased after exercise. Baseline concentrations of ET-1 as well as an increase in soluble E-selectin concentrations 60 min after exercise showed a statistically significant correlation with baseline eosinophil cationic protein, F_ENO and BHR. The increase in plasma concentrations of ET-1 15 min after exercise and soluble E-selectin 60 min after exercise showed a statistically significant correlation with the increase in F_ENO and BHR to histamine 24 h after exercise. Conclusions: We suggest that during EIB changes in the function of pulmonary endothelium occur and these changes may influence inflammation of the airway and remodeling in asthmatic patients.

Changes in High-Sensitivity C-Reactive Protein in Serum and Exhaled Breath Condensate after Intensive Exercise in Patients with Allergic Asthma

“…In asthmatics, changes in endothelial cells could in turn evoke the release of inflammatory mediators and migration of inflammatory cells, and, as a result, lead to intensification of the inflammatory process in airways and bronchial hyperreactivity after exercise [5]. …”

“…Eosinophilic inflammation is also augmented by postexercise bronchoconstriction, which in turn is stimulated by many mediators released mainly by mast cells [4]. We observed an upregulation of airway inflammation, expressed as an increase in exhaled nitric oxide (F ENO ) levels and in bronchial hyperreactivity (BHR) to histamine after postexercise bronchoconstriction in allergic asthma patients [5]. …”

Plasmin System Regulation in an Ovalbumin-Induced Rat Model of Asthma

“…Nevertheless, PAI-1 immunostaining has also been found in endothelial cells. Besides the characteristic changes found in a histological examination of the lungs, we also observed damage to the lung endotheliumwithextensive thinning or total atrophy of endothelial cells.The damage of pulmonary endothelial cells observed in our study may in turn activate the release of various mediators [26] inside the PAI-1, resulting in aggravation of the inflammatory process underway in the airway and, consequently, in airway remodelling. …”

Concomitant Endothelin‐1 Overexpression in Lung Transplant Donors and Recipients Predicts Primary Graft Dysfunction

“…In addition, ET-1 pulmonary tissue mRNA expression was significantly higher (p = 0.01) in Figure 3A) Figure 3C). (27), increased vascular permeability and edema (17,28). Moreover, elevation of tissue ET-1 is associated with hypoxia-mediated vascular resistance (29), and mediates ischemia reperfusioninduced graft edema (17 …”