Vascular dysfunction and chronic obstructive pulmonary disease: the role of redox balance

Abstract

Chronic obstructive pulmonary disease (COPD) is characterized by low pulmonary function, inflammation, free radical production, vascular dysfunction, and subsequently a greater incidence of cardiovascular disease. By administering an acute oral antioxidant cocktail to patients with COPD (n=30) and controls (n=30), we sought to determine the role of redox balance in the vascular dysfunction of these patients. Using a double-blind, randomized, placebo-controlled, crossover design, patients with COPD and controls were ingested placebo or the antioxidant cocktail (vitamin C, vitamin E, α-lipoic acid) after which brachial artery flow-mediated dilation and carotid-radial pulse wave velocity were assessed using ultrasound Doppler. The patients exhibited lower baseline antioxidant levels (vitamin C and superoxide dismutase activity) and higher levels of oxidative stress (thiobarbituic acid reactive species) in comparison with controls. The patients also displayed lower basal flow-mediated dilation (P<0.05), which was significantly improved with antioxidant cocktail (3.1±0.5 versus 4.7±0.6%; P<0.05; placebo versus antioxidant cocktail), but not controls (6.7±0.6 versus 6.9±0.7%; P>0.05; placebo versus antioxidant cocktail). The antioxidant cocktail also improved pulse wave velocity in patients with COPD (14±1 versus 11±1 m·s(-1); P<0.05; placebo versus antioxidant cocktail) while not affecting controls (11±2 versus 10±1 m·s(-1); P>0.05; placebo versus antioxidant). Patients with COPD exhibit vascular dysfunction, likely mediated by an altered redox balance, which can be acutely mitigated by an oral antioxidant. Therefore, free radically mediated vascular dysfunction may be an important mechanism contributing to this population's greater risk and incidence of cardiovascular disease.

Keywords: free radicals; oxidative stress; pulmonary disease, chronic obstructive; vascular stiffness.

Conflict of interest statement

CONFLICTS OF INTEREST: none

Figures

Figure 1. Flow mediated dilation (FMD), expressed as peak relative change in patients with Chronic Obstructive Pulmonary Disease (COPD) as well as age and sex matched controls under placebo and antioxidant conditions

*p < 0.05 COPD vs. control placebo condition, ** p < 0.05 placebo vs. antioxidant in COPD only.

Figure 2. Carotid-Radial Pulse Wave Velocity, under placebo and antioxidant conditions in both patients with Chronic Obstructive Pulmonary Disease (COPD), as well as age and sex matched controls

*p < 0.05 COPD vs. control placebo condition, ** p < 0.05 placebo vs. antioxidant in COPD only. Dashed line indicates the recommended 12 m·s−1 cutoff, as established by the “Reference Values for Arterial Stiffness Collaboration”, indicating elevated risk for cardiovascular disease .

Figure 3. Oxidative stress (Panel A) and antioxidant (Panel B–D) assessments, under placebo and antioxidant conditions in patients with Chronic Obstructive Pulmonary Disease (COPD) as well as age and sex matched controls

* p < 0.05 control vs. COPD placebo condition, **p < 0.05, within group, #p < 0.05 control vs. COPD antioxidant condition.