L. Andrade et al., HYPERCHOLESTEROLEMIA AGGRAVATES RADIOCONTRAST NEPHROTOXICITY - PROTECTIVE ROLE OF L-ARGININE, Kidney international, 53(6), 1998, pp. 1736-1742
It is well known that the radiocontrast-induced ARF depends on risk fa
ctors often associated with compromised renal circulation Since studie
s have shown that endothelium-dependent vasodilation is impaired in hy
percholesterolemia (HC), we studied the effect of radiocontrast (RC) a
dministration (6 ml/kg body wt, via femoral artery) in salt-depleted r
ats that were kept on a normal cholesterol (NC) or HC diet (4% cholest
erol and 1% cholic acid). Inulin clearance (C-In, ml/min/100 g body wt
), renal blood flow (RBF; electromagnetic flowmeter, ml/min/100 g body
wt), and fractional excretions of sodium, potassium and water (FENa,
FEK and FEH2O, respectively), cholesterol (mg/dl), and albumin (g/dl)
were measured 24 hours after radiocontrast administration. The adminis
tration of RC to HC rats (RCHC) resulted in lower values of C-In compa
red with NC rats (RCNC) and control rats: 0.36 +/- 0.085 versus 0.76 /- 0.13 (RCNC; P < 0.01), versus 0.84 +/- 0.03 (control HC; P < 0.01),
versus 0.87 +/- 0.06 (control NC; P < 0.01). Hypercholesterolemia per
se did not alter renal function, and control HC versus control NC was
not significant. Renal blood how was significantly lower in the RCHC
when compared to RCNC (4.3 +/- 0.3 vs. 6.1 +/- 0.3; P < 0.001) and to
control animals (control HC 8.2 +/- 0.3; P < 0.001), and control NC 7.
5 +/- 0.33 (P < 0.001). To study the role of nitric oxide (NO), HC rat
s were treated with an infusion of L-arginine or D-arginine (150 mg vi
a femoral artery) in a 50 mg bolus before RC administration and the re
maining dose continuously for a period of one hour. The administration
of L-arginine to RCHC rats resulted in significantly higher C-In (0.8
6 +/- 0.1; P < 0.001) when compared to the untreated rats (RCHC). D-ar
ginine did not show a significant difference in C-In (0.49 +/- 0.08).
There was a considerable difference between D-arginine RCHC and L-argi
nine RCHC (P < 0.05). The RBF fall was prevented by L-arginine in RCHC
(8.4 +/- 0.23 vs. 4.3 +/- 0.3; P < 0.001), but it was not prevented b
y D-arginine (5.1 +/- 0.57; Pt 0.001). Our data suggest that hyperchol
esterolemia aggravates nephrotoxicity, which is attenuated by L-argini
ne but not by D-arginine administration, suggesting that nitric oxide
plays a significant role in this model of acute renal failure.