Objective: The effects of endothelin-1 (ET-1) on pulmonary vascular tone depend on the complex interplay of ET-1-induced vasoconstriction and vasodilation due to the secondary generation of endothelium-derived vasorelaxants. Therefore, it is likely that the response to ET-1 varies, depending on whether it is applied to the luminal or adventitial side of pulmonary vessels. Therefore, this study was designed to determine the change in luminal ET-1 levels during exercise in patients with chronic obstructive pulmonary disease (COPD).
Methods: All subjects performed a constant-load exercise test for 5 minutes on the ergometer with right heart catheterization while breathing room air or oxygen. ET-1 levels at rest, just after exercise, and 1 hour after exercise were measured in the pulmonary capillary wedge region.
Patients: Thirty-six patients with COPD.
Results: While breathing room air, ET-1 levels did not significantly differ between at rest, just after exercise and 1 hour after exercise [at rest; 4.15 (0.43) pg/ml, just after exercise; 4.15 (0.44) pg/ml, 1 hour after exercise; 4.13 (0.42) pg/ml]. In contrast, while breathing oxygen, ET-1 levels were significantly higher just after exercise [4.41 (0.43) pg/ml] than at rest [3.90 (0.37) pg/ml, p=0.0116] and 1 hour after exercise [3.93 (0.38) pg/ml, p=0.0246]. The change in ET-1 levels between before and just after exercise (delta ET-1) was negatively correlated with change in mPAP (delta mPAP) (r=-0.638, p=0.0001). However, delta ET-1 was not significantly correlated with any FEV1 (% predicted), DLCO, PaO2, or baseline pulmonary hemodynamics.
Conclusion: The impairment of ET-1 release into the luminal side was observed in patients with COPD during exercise while breathing room air. However, oxygen supplementation reversed the capacity of ET-1 release, and delta ET-1 with exercise was negatively correlated with delta mPAP.