Itm. Bloom et al., AN EXPERIMENTAL-STUDY OF ALTERED NITRIC-OXIDE METABOLISM AS A MECHANISM OF CYCLOSPORINE-INDUCED RENAL VASOCONSTRICTION, British Journal of Surgery, 82(2), 1995, pp. 195-198
Nephrotoxicity caused by cyclosporin A (CSA) is the result of vasocons
triction of the renal microcirculation. The endothelium-derived relaxi
ng factor nitric oxide (NO) regulates microvascular blood flow in vari
ous tissues, and mediates the microcirculatory response during hyperte
nsion and sepsis. This study investigated the role of NO in CSA-induce
d renal vasoconstriction. Hydronephrotic kidneys in rats were suspende
d in an environmentally controlled tissue bath, and interlobular, affe
rent and efferent arteriolar diameters and blood flow were measured by
in vivo videomicroscopy. CSA was administered alone, with the nitric
oxide synthase (NOS) inhibitor N-omega-nitro-L-arginine methyl ester (
L-NAME) or with exogenous NOS substrate L-arginine. CSA significantly
constricted the whole of the renal microvasculature whereas L-NAME alo
ne preferentially constricted the preglomerular vessels. L-Arginine re
versed the vasoconstriction induced by CSA whereas L-NAME had no furth
er effect. Preglomerular basal vascular tone is dependent on continuou
s production of NO and alterations in the L-arginine-NO pathway contri
bute to CSA-induced renal vasoconstriction.