Role of nitric oxide in renal hemodynamic abnormalities of cyclosporin nephrotoxicity.
To evaluate the participation of nitric oxide (NO) in chronic cyclosporin A (CsA) nephrotoxicity, the glomerular hemodynamic response to NO inhibition with N-nitro-L-arginine-methyl-ester (NAME) and stimulation of NO production with L-arginine was studied in uninephrectomized rats. Chronic CsA administration produced renal vasoconstriction, characterized by increased afferent (AR) and efferent (ER) resistances, decrease of glomerular plasma flow (QA) and ultrafiltration coefficient (Kf) that resulted in a 53% fall of single-nephron glomerular filtration rate (SNGFR). NAME infusion in vehicle group (V) elevated mean arterial pressure (MAP), AR and ER, reduced qA and Kf, and increased glomerular capillary pressure (PGC), resulting in a 28.9% fall of SNGFR. In the CsA group, NAME also increased MAP, but renal vasoconstriction was more intense; a greater rise of AR lowered PGC (P < 0.05 vs. V) further decreasing SNGFR by 38.9%. In control rats, L-arginine infusion induced a vasodilatory response of AR and ER, and elevation of QA and Kf, which resulted in a 72.6% increase in SNGFR. In the CsA group, greater vasodilation was observed and SNGFR rose by 114.9%. NO2-/NO3- urinary excretion was similar in CsA and V groups, and it was not modified by NAME in either group, but it increased five- to sixfold during L-arginine infusion in both groups. In conclusion, in CsA nephrotoxicity NO production seems to be normal and the ability of the renal endothelium to produce NO is maintained. Therefore renal vasoconstriction associated with CsA is not mediated by NO deficiency, although NO appears to attenuate it.
Bobadilla
N A
NA
Department of Nephrology, Instituto Nacional de Cardiología Ignacio Chávez, México City, México.
Tapia
E
E
Franco
M
M
López
P
P
Mendoza
S
S
García-Torres
R
R
Alvarado
J A
JA
Herrera-Acosta
J
J
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure; D016572:Cyclosporine / Q000633:toxicity*; D005919:Glomerular Filtration Rate; D006439:Hemodynamics / Q000502:physiology*; D007674:Kidney Diseases / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009392:Nephrectomy; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012079:Renal Circulation; D014661:Vasoconstriction / Q000187:drug effects
D009569:Nitric Oxide; D016572:Cyclosporine; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester