Hypertension in cyclosporin A-treated patients is independent of circulating endothelin levels.
OBJECTIVE
To measure blood pressure (BP), plasma endothelin-1 (ET-1), atrial natriuretic peptide (ANP), antidiuretic hormone (ADH) and aldosterone (ALDO) concentration, and plasma renin activity (PRA) in patients treated with a low-dose cyclosporin A (CyA).


METHODS
An open study of patients with rheumatoid arthritis (RA) or palmoplantar pustulosis (PPP).


METHODS
Out-patient clinics at the Central Hospital of Jyväskylä and Helsinki University Central Hospital.


METHODS
CyA was given to 25 patients with RA and to 10 patients with PPP.


METHODS
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 the 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) after 4 months in PPP subjects.


RESULTS
Systolic (sBP) and diastolic blood 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 1-1 to 118 +/- 78 ng 1-1) than in PPP patients (37.3 +/- 26 ng 1-1 to 47.7 +/- 39.9 ng 1-1; P < 0.02). The serum creatinine concentration remained within the normal range, but increased from baseline (76.7 +/- 11.9 mumol 1-1), to 90 +/- 15.4 mumol 1-1 (p < 0.001). The serum magnesium concentration decreased significantly (P < 0.005) after 6 months of CyA treatment in RA patients. No correlation was found between serum creatinine and plasma ET-1 concentration.


CONCLUSIONS
Increased blood pressure during CyA treatment was independent of circulating ET-1 levels. A low dose of CyA did not induce increased ET-1 synthesis as judged from plasma samples. The high plasma ANP level observed in RA patients could be due to fluid retention caused by concomitant treatment with non-steroid anti-inflammatory drugs. Fluid retention and decreased magnesium levels could also be involved in the development of hypertension in CyA-treated subjects.
Forslund
T
T
Department of Internal Medicine, Central Hospital of Jyväskylä, Finland.
Hannonen
P
P
Reitamo
S
S
Fyhrquist
F
F
D000328:Adult; D000450:Aldosterone / Q000097:blood; D001172:Arthritis, Rheumatoid / Q000188:drug therapy; D009320:Atrial Natriuretic Factor / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D016572:Cyclosporine / Q000009:adverse effects* / Q000627:therapeutic use; D016232:Endothelins / Q000097:blood*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000139:chemically induced*; D008297:Male; D008875:Middle Aged; D011565:Psoriasis / Q000188:drug therapy; D012083:Renin / Q000097:blood; D014667:Vasopressins / Q000097:blood
D016232:Endothelins; D014667:Vasopressins; D000450:Aldosterone; D016572:Cyclosporine; D009320:Atrial Natriuretic Factor; D012083:Renin