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A model of nitric oxide tubulovascular cross talk in a renal outer medullary cross section

Department of Chemical and Biological Engineering, Tufts University, Medford, Massachusetts

Submitted 9 June 2006 ; accepted in final form 15 September 2006

We developed a two-dimensional model of NO transport in a cross section of the inner stripe (IS) of the rat outer medulla to determine whether tubular and vascular generation of NO result in significant NO concentration (C_NO) differences between the periphery and the center of vascular bundles and thereby affect medullary blood flow distribution. Following the approach of Layton and Layton (Layton AT, Layton HE. Am J Physiol Renal Physiol 289: F1346–F1366, 2006), the structural heterogeneity of the IS was incorporated in a representative unit consisting of four concentric regions centered on a vascular bundle. Our model suggests that the diffusion distance of NO in the interstitium is limited to a few micrometers. We predict that, under basal conditions, epithelial NO generation raises the average C_NO in pericytes surrounding peripheral descending vasa recta (DVR) by a few nanomoles relative to that in pericytes surrounding central DVR. The short descending limbs and long ascending limbs are found to exert the greatest effect on C_NO in pericytes; long descending limbs and short ascending limbs only have a moderate effect, whereas outer medullary collecting ducts, which are situated far from the vascular bundle center, do not affect pericyte C_NO. Our results suggest that selective stimulation of epithelial NO production should significantly raise the periphery-to-center DVR diameter ratio, thereby increasing the outer medulla-to-inner medulla blood flow ratio. However, concomitant increases in epithelial superoxide (O₂^–) production would counteract this effect. This model confirms the importance of NO and O₂^– interactions in mediating tubulovascular cross talk.

kidney; superoxide; mathematical model; nitric oxide transport