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

https://doi.org/10.1016/j.amjmed.2003.11.022Get rights and content

Abstract

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.

Section snippets

Sample

We included consecutive patients with systemic sclerosis who had been hospitalized for systematic follow-up. Patients were classified as having limited or diffuse cutaneous disease (18). We excluded patients who could not stop vasodilator therapy, as well as those who were pregnant or current smokers, or who had diabetes, hypercholesterolemia, or severe disease (e.g., cardiac or hepatic failure, cancer, or gangrene). We also excluded patients who had not been stable on their current treatment

Results

We included 42 successive systemic sclerosis patients (38 [90%] women; mean [± SD] age, 54 ± 12 years). All patients had Raynaud's phenomenon (Table 1). The control group of 23 healthy subjects included 20 (87%) women, with a mean age of 49 ± 10 years. Of the 19 patients included in the long-term evaluation, 16 (84%) were women; they had a mean age of 58 ± 12 years and a mean disease duration of 8 ± 8 years, and 12 (63%) had limited cutaneous disease.

Discussion

Our data demonstrate excessive oxidative stress in patients with systemic sclerosis after cessation of dihydropyridine treatment (at baseline). In addition, we found a substantial acute and sustained decrease in oxidative stress after treatment with a dihydropyridine.

We chose different markers to explore different aspects of oxidative stress. Carbonyl residues are well-accepted markers of protein oxidation, whereas advanced oxidation protein products have been validated more recently. In our

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    This work was partly supported by a grant from Association des Sclérodermiques de France.

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