Abstract：
OBJECTIVE:Antiphospholipid antibodies are associated with increased risk of thrombosis, particularly as in antiphospholipid syndrome. This study aims to determine the acute effects of anticardiolipin antibodies on nitric oxide production and vascular function. METHODS:Ex vivo aortic rings from male Sprague Dawley rats were incubated with IgG monoclonal anticardiolipin antibody (IS4) or a non-specific IgG control. In organ baths, response to phenylephrine and acetlycholine was determined alone and with nitro-L-arginine methyl ester (L-NAME), 1,400 W, D-arginine, L-arginine, sodium nitroprusside and cardiolipin. In vivo antibodies were injected into anaesthetised, spontaneously breathing male Sprague Dawley rats. Haemodynamic variables and serum nitric oxide were measured. Immunohistochemistry for iNOS and eNOS was performed in kidney vessels. RESULTS:Phenylepherine contraction was decreased in the IS4 group compared to controls (p < 0.001). L-NAME, 1,400 W and cardiolipin, abolished this effect. L-Arginine caused significant relaxation in the IS4 group (p = 0.005). Mean arterial pressure in rats injected with IS4 was reduced compared to IgG and saline controls (p < 0.001). NO in plasma increased significantly after IS4 administration (p < 0.001). Immunohistochemistry showed increased iNOS expression in kidney arteries in the IS4 group, with no change in eNOS. CONCLUSION:Anticardiolipin antibodies induce NO production acutely via increased expression of iNOS in both ex vivo and in vivo models.
journal_name
Atherosclerosisjournal_title
Atherosclerosisauthors
Alves JD,Clapp BR,Stidwill R,Chen PP,Hingorani AD,Singer M,Isenberg DAdoi
10.1016/j.atherosclerosis.2005.06.044keywords:
subject
Has Abstractpub_date
2006-04-01 00:00:00pages
246-53issue
2eissn
0021-9150issn
1879-1484pii
S0021-9150(05)00398-9journal_volume
185pub_type
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