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Cyclosporin-induced hypertension precedes renal dysfunction and sodium retention in man
N D Sturrock1, C C Lang, A D Struthers
1Department of Clinical Pharmacology, Ninewells Hospital and Medical School, Dundee, UK.
Objective:
To study the acute effects of cyclosporin on blood pressure, renal function and hormones within the first few hours of drug ingestion in healthy man.
Design:
A therapeutic (12 mg/kg) and a supratherapeutic (30 mg/kg) dose of cyclosporin were administered orally to 10 salt-replete normal healthy volunteers. Their renal haemodynamic parameters were assessed by inulin and para-aminohippurate clearances, and their blood pressure was recorded every 20 min.
Results:
Cyclosporin had an acute hypertensive effect while having no effect on sodium excretion or renal function. The earliest renal effect of cyclosporin was on water handling, with a marked antidiuretic effect.
Conclusions:
Our findings contradict previous data and currently held views regarding the pathogenesis of cyclosporin-induced hypertension. In particular, we have demonstrated that hypertension precedes any measurable change in renal haemodynamic parameters and occurs without apparent overall alterations in renal sodium excretion. We have also found that an antidiuresis is a very early renal effect of cyclosporin.