Forslund T, Hannonen P, Reitamo S, Fyhrquist F
Department of Internal Medicine, Central Hospital of Jyväskylä, Finland.
J Intern Med. 1995 Jul;238(1):71-5. doi: 10.1111/j.1365-2796.1995.tb00901.x.
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).
An open study of patients with rheumatoid arthritis (RA) or palmoplantar pustulosis (PPP).
Out-patient clinics at the Central Hospital of Jyväskylä and Helsinki University Central Hospital.
CyA was given to 25 patients with RA and to 10 patients with PPP.
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.
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.
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.
测定接受小剂量环孢素A（CyA）治疗患者的血压（BP）、血浆内皮素-1（ET-1）、心房利钠肽（ANP）、抗利尿激素（ADH）和醛固酮（ALDO）浓度以及血浆肾素活性（PRA）。
对类风湿关节炎（RA）或掌跖脓疱病（PPP）患者进行的一项开放性研究。
于韦斯屈莱中心医院和赫尔辛基大学中心医院的门诊。
25例RA患者和10例PPP患者接受了CyA治疗。
在研究开始时和6个月后，RA患者分别接受剂量为2.5±0.13mg/kg体重（BW）至3.47±0.79mg/kg BW（平均值±标准差）的CyA，PPP患者在4个月后CyA剂量从2.67±0.13mg/kg BW降至2.07±0.96mg/kg（P<0.001）。
在研究期间，收缩压（sBP）和舒张压（dBP）从127.8±13.6/79.7±8.4mmHg升高至140.0±19.8/83.8±9.7mmHg（P<0.03）。在CyA治疗的4至6个月期间，血浆ET-1、ANP、ALDO和ADH浓度以及PRA未发生变化。接受CyA治疗的RA患者血浆ANP浓度（112±87ng/L至118±78ng/L）始终高于PPP患者（37.3±26ng/L至47.7±39.9ng/L；P<0.02）。血清肌酐浓度保持在正常范围内，但从基线水平（76.7±11.9μmol/L）升高至90±15.4μmol/L（P<0.001）。在RA患者中，CyA治疗6个月后血清镁浓度显著降低（P<0.005）。未发现血清肌酐与血浆ET-1浓度之间存在相关性。
CyA治疗期间血压升高与循环ET-1水平无关。从小剂量CyA治疗的血浆样本判断，其未诱导ET-1合成增加。RA患者中观察到的高血浆ANP水平可能归因于同时使用非甾体抗炎药引起的液体潴留。液体潴留和镁水平降低也可能与CyA治疗患者高血压的发生有关。
