Effect of prostaglandin E administration in a nephrotoxic and a vasoconstrictor model of acute renal failure

Abstract

It is generally thought that renal vasoconstriction is involved in the generation of acute renal failure (ARF). To test this hypothesis, two models of experimental ARF, uranyl nitrate-induced ARF and the unilateral infusion of norepinephrine, were investigated. Prior to the induction of acute renal failure, renal blood flow (RBF) was markedly increased in one kidney by the intrarenal infusion of prostaglandin E2 (PGE). In the uranyl nitrate studies, RBF in the PGE-infused kidney was markedly elevated throughout the three-hour period after administration of the nephrotoxic drug. Mean values were 171 ml/min prior to PGE infusion and 308 ml/min three hours after the administration of uranyl nitrate (P < 0.005), while in the control kidney, blood flow fell slightly from 164 to 143 ml/min. The fractional distribution of blood flow to the outer cortex, measured with radioactive microspheres, decreased significantly (P < 0.05) in the PGE-infused kidney but remained unchanged in the control kidney three hours after uranyl nitrate infusion. In spite of these differences in total and regional blood flow, inulin clearance fell similarly in both kidneys at three hours from 40 to 24 (P < 0.005) and 43 to 28 ml/min (P < 0.005) in the PGE-infused and control kidney, respectively. Utilizing a similar protocol, inulin clearance was reduced equally in both kidneys 48 hr after uranyl nitrate infusion. In the norepinephrine studies, RBF was reduced to an undetectable level, as measured by flowmeter during the administration of the vasoconstrictor, and inulin clearance was decreased to 7% of the control value three hours after the infusion of norepinephrine (P < 0.001). When PGE was administered prior to and during norepinephrine infusion, RBF was similarly decreased during norepinephrine, but inulin clearance was reduced to a lesser extent three hours after discontinuing the vasoconstrictor than when norepinephrine was given alone, -48% vs. -93% (P <0.005). Infusion of PGE prior to, during, and for the three hour period after norepinephrine had a similar protective effect, even though renal hemodynamics was more rapidly and completely restored in this model. When PGE was given only during the norepinephrine infusion, inulin clearance fell as much as it did with norepinephrine alone. These findings indicate that marked renal vasodilatation does not obviate the acute reduction in inulin clearance after uranyl nitrate infusion. In contrast, a prior infusion of PGE does attenuate the development of renal functional impairment after intrarenal norepinephrine, even though the vasodilator does not alter the marked increase in renal resistance during norepinephrine infusion.