The distribution of catecholamines between plasma and platelets in cyclosporin A-induced hypertensive rats

One of the most serious side effects of the immunosuppressive agent, cyclos porin A (CsA), is drug-related hypertension. As it is generally accepted, t he sympathetic nervous system may play an important role in the development or maintenance of this abnormal pathophysiological situation. This study i s aimed at assessing plasma and platelet catecholamines, and a possible con nection to cyclosporin A-induced increased arterial blood pressure. It was thus based on an investigation in which Wistar rats were divided into three groups: one taking only orange juice (control) and the other two receiving 5 and 30 mg kg(-1) ('trough' and 'peak') of cyclosporin A (Sandimmun Neora l(R)), daily, for 7 weeks. Plasma and platelet noradrenaline, adrenaline an d dopamine levels and arterial blood pressures were evaluated before the st art of the study (week 0) and after 2, 4 and 7 weeks. Plasma and platelet c atecholamines increased drastically in the 'peak' CsA concentration-treated group, which contrasts with the slight decrease observed in the group trea ted with the 'trough' concentration. However, both groups revealed an incre ase in blood pressures, when compared with the control group. These finding s suggest that at least 'peak' cyclosporin A concentration alters significa ntly the plasma and platelets catecholamines levels, which may contribute t o the cyclosporin A-induced hypertension. Other contributions, regardless o f catecholamine content disturbances, might occur, at least at 'trough' CsA concentrations. (C) 2000 Academic Press.