L-ARGININE REVERSES THE ANTINATRIURETIC EFFECT OF CYCLOSPORINE IN RENAL-TRANSPLANT PATIENTS

Background. Cyclosporin has been shown to facilitate renal vasoconstri ction and to have an antinatriuretic effect. The existence of an inter ference of cyclosporin with the vasodilating properties of endothelium mediated by nitric oxide production could mediate these effects. On t he other hand, the infusion of the nitric oxide precursor L-arginine h as been shown to induce renal vasodilatation and to facilitate natriur esis in normal volunteers. We have investigated the renal effects of t he administration of an infusion of L-arginine in renal transplant pat ients chronically treated with cyclosporin. To facilitate the analysis of the data the effects of the administration of a similar dose of cy closporin on renal function during the infusion of a vehicle were also investigated during the administration of a vehicle of L-arginine. De sign. Ten male renal transplant patients, chronically treated with cyc losporin and with a stable renal function were studied during 2 consec utive days after the administration of the usual morning dose of cyclo sporin. The first day they received an intravenous infusion of vehicle and the second the infusion of graded doses of L-arginine (50, 100, 1 50 mg/kg/h) during 3 consecutive h. Results. The first day, after cycl osporin administration a significant fall (P<0.01) was observed in nat riuresis and kaliuresis in the absence of changes in renal plasma flow and glomerular filtration rate. After the administration of L-arginin e significant (P<0.01) increases of renal plasma flow, glomerular filt ration rate, and natriuresis were seen. The increase in blood levels o f cyclosporin after its administration did not differ between days 1 a nd 2. Conclusion. These results indicate that L-arginine facilitates r enal vasodilatation and natriuresis in renal transplant patients. Furt hermore, the observed increase in sodium excretion could indicate that L-arginine counteracts the antinatriuretic effect of cyclosporin.