Acute and sustained effects of dihydropyridine-type calcium channel antagonists on oxidative stress in systemic sclerosis

Purpose To evaluate the potential antioxidant properties of dihydropyridine calcium channel antagonists in systemic sclerosis. Methods Forty-two patients with systemic sclerosis were included (mean [± SD] age, 54 ± 12 years; mean disease duration, 8 ± 7 years). Plasma markers of oxidative stress (carbonyl residues, advanced oxidation protein products, malondialdehyde, nitrosothiols, and total thiol groups) were determined 72 hours after the discontinuation of usual dihydropyridine treatment (with either nifedipine or nicardipine), shortly after reinitiation of treatment, and 9 to 12 months later (long-term treatment) in 19 of the patients. Baseline values were compared with those in 23 healthy volunteers. Results Mean levels of plasma markers of oxidative stress were much higher in patients with systemic sclerosis than in controls (carbonyls, 0.4 ± 0.1 nmol/mg protein vs. 0.3 ± 0.1 nmol/mg protein, P = 0.0001; advanced oxidation protein products, 111 ± 13 μmol/L vs. 47 ± 7 μmol/L, p = 0.003; malondialdehyde, 11.3 ± 3.3 μmol/L vs. 5.5 ± 1.3 μmol/L, P<0.0001; nitrosothiols, 1.6 ± 0.2 μmol/L vs. 0.6 ± 0.2 μmol/L, P<0.0001). In contrast, thiol levels were lower in systemic sclerosis patients (264 ± 80 μmol/L vs. 435 ± 50 μmol/L, P<0.0001). Short-term treatment led to a significant decrease in oxidative stress markers (carbonyls, 0.3 ± 0.1 nmol/mg protein, P<0.0001), advanced oxidation protein products (60 ± 3 μmol/L, P<0.0001), malondialdehyde (8.8 ± 5.6 μmol/L, p = 0.0002), and nitrosothiols (1.4 ± 0.2 μmol/L, p = 0.0001), but an increase in thiol levels (340 ± 84 μmol/L, P<0.0001). These decreases persisted with long-term treatment. Conclusion Dihydropyridines significantly decrease oxidative stress in systemic sclerosis patients, in both the short and long term.