Renal hemodynamic effects of L-arginine and sodium nitroprusside in heart transplant recipients.
BACKGROUND
Long-term treatment with cyclosporine A (CsA) induces vasoconstriction in the kidney and causes renal impairment. An altered L-arginine (L-Arg)/nitric oxide (NO) pathway may play a key role in CsA nephrotoxicity.


METHODS
We studied the effect of L-Arg (dosage, 17 mg/kg/min over 30 min), the precursor of NO synthesis, and sodium nitroprusside (SNP; dosage, 1.0 microgram/kg/min over 30 min) on renal hemodynamics in a double-blind, placebo-controlled, randomized, three-way cross-over study comprising 12 stable cardiac transplant recipients on long-term CsA treatment, 10 patients with chronic nephropathy not receiving CsA, and 13 healthy controls. Renal plasma flow (RPF) and glomerular filtration rate (GFR) were measured by paraaminohippurate (PAH) and the inulin clearance method, respectively.


RESULTS
In healthy subjects, L-Arg induced an increase in RPF (P = 0.009) and GFR (P = 0.001). By contrast, L-Arg did not induce renal hemodynamic effects in heart transplant patients or patients with chronic nephropathy. SNP reduced RPF (P = 0.050) and GFR (P = 0.005) in patients with chronic nephropathy but did not affect renal hemodynamics in heart transplant recipients or in healthy subjects.


CONCLUSIONS
These data indicate that L-Arg cannot be used to reverse CsA-induced renal vasoconstriction in heart transplant recipients under long-term CsA treatment, although these patients have a normal renal response to SNP.
Koller-Strametz
J
J
Department of Clinical Pharmacology, University of Vienna, Austria.
Wolzt
M
M
Fuchs
C
C
Putz
D
D
Wisser
W
W
Mensik
C
C
Eichler
H G
HG
Laufer
G
G
Schmetterer
L
L
D000368:Aged; D001120:Arginine / Q000008:administration & dosage*; D001794:Blood Pressure / Q000187:drug effects; D002908:Chronic Disease; D015331:Cohort Studies; D016572:Cyclosporine / Q000009:adverse effects; D005919:Glomerular Filtration Rate; D016027:Heart Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects; D007275:Injections, Intravenous; D007668:Kidney / Q000098:blood supply; D007674:Kidney Diseases / Q000139:chemically induced / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000032:analysis; D009599:Nitroprusside / Q000008:administration & dosage*; D012079:Renal Circulation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000008:administration & dosage*
D007166:Immunosuppressive Agents; D014665:Vasodilator Agents; D009599:Nitroprusside; D009569:Nitric Oxide; D016572:Cyclosporine; D001120:Arginine