HYPERTENSION CYCLOSPORINE A-TREATED PATIENTS IS INDEPENDENT OF CIRCULATING ENDOTHELIN LEVELS

Objectives. To measure blood pressure (BP), plasma endothelin-1 (ET-1) , atrial natriuretic peptide (ANP), antidiuretic hormone (ADH) and ald osterone (ALDO) concentration, and plasma renin activity (PRA) in pati ents treated with a low-dose cyclosporin A (CyA). Design. An open stud y of patients with rheumatoid arthritis (RA) or palmoplantar pustulosi s (PPP). Setting. Out-patient clinics at the Central Hospital of Jyvas kyla and Helsinki University Central Hospital. Subjects. CyA was given to 25 patients with RA and to 10 patients with PPP. Intervention. RA patients were given CyA at a dose of 2.5+/-0.13 mg kg(-1) body weight (BW) to 3.47+/-0.79 mg kg(-1) BW (mean values+/-SD) at the start of th e study and after 6 months, respectively, and the CyA dose was 2.67+/- 0.13 mg kg(-1) BW decreasing to 2.07+/-0.96 mg kg(-1) (P < 0.001) afte r 4 months in PPP subjects. Results. Systolic (sBP) and diastolic bloo d pressure (dBP) increased from 127.8+/-13.6/79.7+/-8.4 mmHg to 140.0/-19.8/83.8+/-9.7 mmHg during the study (P < 0.03). Plasma ET-1, ANP, ALDO and ADH concentration and PRA did not change during 4 to 6 months of CyA treatment. The plasma ANP concentration was constantly higher in CyA-treated RA patients (112+/-87 ng l(-1) to 118+/-78 ng l(-1)) th an in PPP patients (37.3+/-26 ng l(-1) to 47.7+/-39.9 ng l(-1); P < 0. 02). The serum creatinine concentration remained within the normal ran ge, but increased from baseline (76.7+/-11.9 mu mol l(-1)), to 90+/-15 .4 mu mol l(-1) (p < 0.001). The serum magnesium concentration decreas ed significantly (P < 0.005) after 6 months of CYA treatment in RA pat ients. No correlation was found between serum creatinine and plasma ET -1 concentration. Conclusions. Increased blood pressure during CBA tre atment was independent of circulating ET-1 levels. A low dose of CyA d id not induce increased ET-1 synthesis as judged from plasma samples. The high plasma ANP level observed in EW patients could be due to flui d retention caused by concomitant treatment with non-steroid anti-infl ammatory drugs. Fluid retention and decreased magnesium levels could a lso be involved in the development of hypertension in CyA-treated subj ects.