title: Effect of Cyclosporin A on prostacyclin synthesis by vascular tissue.
abstract: NZW rabbits with acute serum sickness given Cyclosporin A (CyA) 25 mg/kg/day develop glomerular capillary thrombosis similar to that seem 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 +/- 6.9 ng 6-keto PGF1 alpha/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 +/- 0.5 ng/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.
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism*; D003524:Cyclosporins / Q000494:pharmacology*; D011464:Epoprostenol / Q000096:biosynthesis*; D006463:Hemolytic-Uremic Syndrome / Q000378:metabolism*; D010974:Platelet Aggregation / Q000187:drug effects; D011817:Rabbits
chemical_list: D003524:Cyclosporins; D011464:Epoprostenol