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This study was undertaken to examine the possible role of endothelium-derived relaxing factor (EDRF), identified as nitric oxide (NO), in the pathogenesis of radiocontrast-induced acute renal failure in rats. Normal and salt-depleted rats were monitored for 60 min or 24 h after radiocontrast administration. The administration of L-arginine to normal rats abolished the immediate decrease in p-aminohippurate clearance (CPAH) and attenuated the decrease in inulin clearance (CIn). The administration of NO synthase inhibitor to the salt-depleted animals resulted in a significantly more pronounced decrease in CPAH compared with both the control and the L-arginine-treated animals. The recovery of CIn 24 h after radiocontrast administration to the salt-depleted rats was significantly better in the L-arginine-treated rats than in either the control or inhibitor-treated groups. The administration of radiocontrast material resulted in a significant decrease in urinary guanosine 3',5'-cyclic monophosphate as well as NO2 + NO3 excretion. This decrease was significantly attenuated by L-arginine. Our results 1) suggest that NO plays a major role in the pathogenesis of radiocontrast-induced acute renal failure and 2) suggest a novel therapeutic approach, i.e., the use of L-arginine in this form of acute renal failure.

Renal and cardiac effects of norepinephrine and dopamine were evaluated in swine aged 1 wk, 2 wk, and 6 mo. The swine were anesthetized with pentobarbital (20-30 mg/kg). Aortic pressure, right ventricular pressure and its first derivative, and heart rate were recorded, together with carotid and renal (RBF) arterial flows. Glomerular filtration rate (GFR) was determined by [14C]inulin clearance. After a control period, norepinephrine or dopamine was infused intravenously for 10-20 min before and then during another clearance period. After a second control period, the second catecholamine was infused. GFR increased in piglets given either catecholamine. Norepinephrine at equipressor doses (2.0 micrograms.kg-1.min-1 in piglets and 1.0 micrograms.kg-1.min-1 in mature swine) decreased RBF and increased renal resistance. Dopamine at equi-inotropic doses (10 micrograms.kg-1 min-1 in piglets and 20 micrograms.kg-1.min-1 in mature swine) increased RBF and decreased renal resistance only in mature swine. Infusions of dopamine at a low dose (5 micrograms.kg-1.min-1) also failed to increase RBF or decrease renal resistance in piglets. The results suggest that maturation of the mechanism of renal vasodilation by dopamine occurs later than that for vasoconstriction by norepinephrine.