Progressive Development of Renal Vascular Dysfunction in Brain Death Implicates Reversible Alterations of Nitric Oxide Metabolism

Abstract

Background Vascular endothelial dysfunction occurs in the kidney graft from marginal brain death (BD) donors and may be responsible for a low success rate after transplantation. Methods BD was induced in 16 dogs for 6 hours. Immediately after the inflation of the intracranial balloon, the treated group (n = 8) received 40 mg/kg bolus followed by 3 mg/kg/min infusion of L-arginine for 30 minutes. Renal vascular function and hemodynamic and biochemical parameters were determined. Results BD caused vasoconstriction, increase in renal venous nitrite (4.9 ± 0.8 versus 2.6 ± 0.1, P < .05) and myeloperoxidase levels (1.43 ± 0.04 versus 2.43 ± 0.23, P < .001), and reduced vasodilatation of renal artery to acetylcholine. Larginine diminished the renal vasoconstriction induced by 6 hour BD (RVR = 0.92 ± 0.06 versus 1.38 ± 0.003 in controls, P < .05), maintained renal oxygen extraction in physiological range (17.5 ± 4.6% versus 25.4 ± 2.9% in controls, P < .05) and prevented the rise of myeloperoxidase (1.69 ± 0.19, P < .05 versus controls) and nitrite levels (3.3 ± 0.5, P < .05), followed by preservation of endothelium dependent vasodilatation ( P < .05 versus controls). Conclusions The findings suggest that exogenous L-arginine supplementation may preserve endothelial vascular function in the kidney before prelevation from marginal BD donors.