To evaluate the association of cyclosporine (CsA)-related nephrotoxicity with nitric oxide (NO) and endothelin, the effects of L-arginine (LA) and branched-chain amino acid (BCAA) infusions on renal hemodynamics in 5 normal volunteers and 12 renal transplant recipients were assessed. In normal humans, LA, but not BCAA, reduced mean arterial pressure and renal vascular resistance while increasing RPF and urinary nitrate (NO3-) excretion. Group 1 included six transplant recipients not on CsA; Group 2 subjects (N = 6) were receiving CsA. In both groups, mean arterial pressure declined during the infusion of LA (116 +/- 4 to 109 +/- 4 mm Hg; P < 0.001) but not BCAA (116 +/- 3 to 115 +/- 3; P = not significant). In Group 1, LA increased RPF 33 +/- 13% (329 +/- 48 to 436 +/- 77 mL/min per 1.73 m2; P = 0.01) and GFR 37 +/- 16% (95 +/- 7 to 130 +/- 18 mL/min per 1.73 m2; P = 0.01); renal vascular resistance declined 27 +/- 6%. In Group 2, LA did not affect renal hemodynamics. No changes occurred with BCAA in either group. LA increased urinary NO3-excretion by 27 +/- 17% in Group 1 (P < 0.05), but only by 16 +/- 13% in Group 2 (P = not significant). Urinary endothelin excretion was higher in Group 2 subjects (10.1 +/- 1.3 versus 5.3 +/- 0.8 pg/mL of GFR, P < 0.01). LA-induced renal vasodilation is associated with the increased urinary excretion of NO3-.(ABSTRACT TRUNCATED AT 250 WORDS)