Objective: This work aims to study the cardiovascular and renal effects of cyclosporin treatment. This purpose was achieved by using an animal model treated with cyclosporin in doses equivalent to the Cmin and Cmax values from human pharmacokinetics.
Methods: Wistar rats, weighing between 300 and 400 g, were treated with cyclosporin (Sandimmune Neoral) for 7 weeks. The cyclosporin was diluted in orange juice and administered in two doses: 5 and 30 mg/kg/day. The control group received only orange juice. Blood pressure was evaluated by the tail-cuff method and an ECG was also performed. Besides blood cyclosporin levels, CPK, LDH, SGPT, SGOT, sodium, potassium and creatinine in serum and protein in urine, as well as plasma lipids (triglycerides, total and HDL cholesterol), were measured.
Results: Both doses of cyclosporin increased blood pressure but only 30 mg/kg/day induced tachycardia. Changes in electrocardiographic profile were also observed: an increase in QTc as well as an increase in T wave amplitude. Thus, the group treated with 30 mg/kg/day of cyclosporin showed an ischemic heart disease electrocardiographic profile which was reinforced by increased CPK, SGPT and SGOT but with no changes in LDH values. None of the cyclosporin-treated rats presented cardiac hypertrophy. Despite the increase in plasma lipids there was little or no increase in body weight, which was most evident in the group that received 30 mg/kg/day of cyclosporin. No alterations were observed in serum Na+, K+ or creatinine values or in urine protein levels.
Conclusions: Our results showed that the cardiovascular effects of cyclosporin in Wistar rats are characterized by arterial hypertension, ischemic heart disease and tachycardia, but not cardiac hypertrophy. However, when these changes occur, kidney function seems to be normal. These facts suggest that cyclosporin-induced cardiovascular changes, particularly hypertension, are prior to renal damage. Moreover, our cyclosporin-induced hypertension model could be useful to study drugs that could treat or prevent these changes.