L-arginine reverses the antinatriuretic effect of cyclosporin in renal transplant patients

BACKGROUND: Cyclosporin has been shown to facilitate renal vasoconstrictionand to have an antinatriuretic effect. The existence of an interference ofcyclosporin with the vasodilating properties of endothelium mediated bynitric oxide production could mediate these effects. On the other hand, theinfusion of the nitric oxide precursor L-arginine has been shown to inducerenal vasodilatation and to facilitate natriuresis in normal volunteers. Wehave investigated the renal effects of the administration of an infusion ofL-arginine in renal transplant patients chronically treated withcyclosporin. To facilitate the analysis of the data the effects of theadministration of a similar dose of cyclosporin on renal function duringthe infusion of a vehicle were also investigated during the administrationof a vehicle of L-arginine. DESIGN: Ten male renal transplant patients,chronically treated with cyclosporin and with a stable renal function werestudied during 2 consecutive days after the administration of the usualmorning dose of cyclosporin. The first day they received an intravenousinfusion of vehicle and the second the infusion of graded doses ofL-arginine (50, 100, 150 mg/kg/h) during 3 consecutive h. RESULTS: Thefirst day, after cyclosporin administration a significant fall (P <0.01) was observed in natriuresis and kaliuresis in the absence of changesin renal plasma flow and glomerular filtration rate. After theadministration of L-arginine significant (P < 0.01) increases of renalplasma flow, glomerular filtration rate, and natriuresis were seen. Theincrease in blood levels of cyclosporin after its administration did notdiffer between days 1 and 2. CONCLUSION: These results indicate thatL-arginine facilitates renal vasodilatation and natriuresis in renaltransplant patients. Furthermore, the observed increase in sodium excretioncould indicate that L-arginine counteracts the antinatriuretic effect ofcyclosporin.