HYPERCHOLESTEROLEMIA AGGRAVATES RADIOCONTRAST NEPHROTOXICITY - PROTECTIVE ROLE OF L-ARGININE

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.