NZW rabbits with acute serum sickness given Cyclosporin A (CyA) 25 mg/kg/day develop glomerular capillary thrombosis similar to that seen in the haemolytic uraemic syndrome (HUS). Bone marrow recipients treated with CyA may also develop a similar renal lesion associated with a haemolytic uraemic-like syndrome. In the HUS, impaired production of prostacyclin by vascular tissue may be found and has been associated with a lack of a plasma factor which stimulates prostacyclin synthesis. We therefore examined, in six normal rabbits, treated with CyA 25 mg/kg for five days, the ability of plasma from treated and untreated rabbits to stimulate prostacyclin synthesis from normal rabbit aortic rings. Plasma from untreated rabbits produced 21.5 ± 6.9ng 6-keto PGFlα/ml/mg wet weight aorta (mean ± SEM). However, the ability of plasma from CyA-treated rabbits to stimulate prostacyclin production was profoundly reduced. This was apparent within 24 hours of starting and persisted for seven days after therapy was stopped: mean of values from all rabbits bled from start of therapy until seven days after therapy stopped was 3.7 ± 0.5ng/ml/mg. We suggest that the renal complications of CyA therapy are related to a failure of normal vascular prostacyclin synthesis due to lack of a prostacyclin-stimulating plasma factor.
- Cyclosporin A
- Vascular endothelium
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine