Background/Purpose:

Antimalarial drugs are a cornerstone of treatment of systemic lupus erythematosus (SLE). It has been suggested that antimalarial drugs may have a protective effect on thrombosis, may be beneficial on lipid profile, may reduce atherosclerosis accrual.

In the present study we aimed at assessing the endothelial function on mesenteric resistance arteries in a mouse model of SLE (NZB/W F1) treated with hydroxychloroquine (HCQ).

Methods:

Sixty 12 weeks old female NZB/W F1 mice (mSLE) were divided in 3 groups: group A no therapy, Group B treated with HCQ 3 mg/Kg body weight/day (corresponding to 200 mg/day in humans), group C C56BL/6J (mC) mice as controls. Animals were monitored for 24-hours proteinuria, anti-dsDNA antibodies titers as disease progression parameters and were sacrificed at 18, 24, 30 and 42 weeks of age.

Endothelium-dependent relaxation of small arteries (pressurized myograph), was assessed by infusion of acetylcholine (Ach), while NO availability was assessed by repeating Ach under the nitric oxide synthase (NOS) inhibitor L-NAME.

Results: In Group A, a decline in relaxation to Ach emerged at 18 weeks of age, with a further worsening at 30 and 42. The inhibitory effect of L-NMMA on Ach was reduced at 18 and progressively blunted up to 30 and 42 weeks; interestingly, endothelial dysfunction (ED) appeared simultaneously to a significant increase in 24-hours proteinuria. In group B, HCQ treatment was associated with a significant delay in the appearance of anti-dsDNA and proteinuria and concomitantly, HCQ prevented the decline of Ach-induced relaxation up to 30 weeks. Starting from this age, the protective effect of HCQ, although still present, was less evident. In group C, relaxation to Ach significantly started to decline at 30 weeks of age with a concomitant reduction of the inhibitory effect of L-NMMA on Ach. The response to sodium nitroprusside (SNP) started to decline at 30 weeks of age in Group A, while was preserved in group C (table 1).

Conclusion: Treatment with HCQ seems to prevent the occurrence of ED in treated animals, suggesting an early vascular protective effect of this drug. Additional studies are underway to understand whether this observation has to be correlated with disease activity control or reflects an additional independent effect of HCQ.

Table 1. ED relaxation

Age (weeks)

18

24

30

42

Group A

Group B

Group C

Group A

Group B

Group C

Group A

Group B

Group C

Group A

Group B

Group C

Maximal vasodilation to Ach (%)

90±2

98±2

98±2

81±2

95±1

98±1

69±2

87±1

93±1

63±2

71±1

83±1

Inhibitory effect of L -NMMA  on Ach (%)

42±1

Not done

52±3

30±2

Not done

54±3

10±1

Not done

44±1

7±4

Not done

35±2

Maximal vasodilation to SNP (%)

99±2

Not done

97±3

97±2

Not done

98±2

85±3

Not done

94±2

76±1

Not done

83±2

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/effects-of-in-vivo-treatment-with-hydroxychloroquine-on-endothelial-function-in-a-murine-model-of-systemic-lupus-erythematosus/