Effect of dietary supplementation with fish oil on cyclosporine A-induced vascular toxicity.

We wished to determine whether dietary supplementation with fish oil prevents the vascular toxicity of cyclosporine (Cx). In a first set of experiments, we assessed the endothelial function of aortas isolated from rats supplemented for 6 weeks with fish oil (FO), administered by gavage, and providing 150 mg/kg/day of eicosapentaenoic acid and 100 mg/kg/day of docosahexaenoic acid. FO treatment altered neither acetylcholine- and histamine-induced relaxations, nor serotonin-induced contractions (NS vs. control group). Thereafter, three groups of rats were treated in parallel. Group 1 received FO supplementation (by gavage) for 6 weeks, and Cx (10 mg/kg/day po) was added during the last 2 weeks, group 2 received Cx only (10 mg/kg/day po) for 2 weeks, and group 3 served as a control. Both acetylcholine-and histamine-induced relaxations were reduced in group 2 compared with the control group, as indicated by the area under the curve (AUC), which was significantly higher: 296 +/- 17 vs. 138 +/- 32, and 392 +/- 38 vs. 318 +/- 25 for acetylcholine and histamine, respectively. In group 1, AUC for acetylcholine remained significantly different from the control (241 +/- 31 vs. 138 +/- 32), whereas AUC for histamine was 367 +/- 28 (NS vs. control). The serotonin-induced contractions were also enhanced in group 2 compared with those of the control group, and this alteration was not attenuated in group 1. After mechanical removal of the endothelium, the increased responsiveness to serotonin persisted in groups 1 and 2, suggesting this functional alteration to be located in the smooth muscle cells. Thus, in the rat the attenuation of Cx-induced vascular toxicity by fish oil supplementation is only partial, that is, it involves a slight improvement in endothelial function, but with persistence of functional changes in smooth muscle.