Determinants of basal nitric oxide concentration in the renal medullary microcirculation.
In this study, we modeled the production, transport, and consumption of nitric oxide (NO) in the renal medullary microcirculation under basal conditions. To yield agreement with reported NO concentrations of approximately 60-140 nM in medullary tissues (Zou AP and Cowley AW Jr. Hypertension 29: 194-198, 1997; Am J Physiol Regul Integr Comp Physiol 279: R769-R777, 2000) and 3 nM in plasma (Stamler JS, Jaraki O, Osborne J, Simon DI, Keaney J, Vita J, Singel D, Valeri CR, and Loscalzo J. Proc Natl Acad Sci USA 89: 7674-7677, 1992), the permeabilities of red blood cells (RBCs), vascular walls, and pericytes to NO are all predicted to lie between 0.01 and 0.1 cm/s, and the NO production rate by vasa recta endothelium is estimated to be on the order of 10(-14) mumol.mum(-2).s(-1). Our results suggest that the concentration of NO in RBCs, which is essentially controlled by the kinetics of NO scavenging by hemoglobin, is approximately 0.01 nM, that is, 10(3) times lower than that in plasma, pericytes, and interstitium. Because the basal concentration of NO in pericytes is on the order of 10 nM, it may be too low to active guanylate cyclase, i.e., to induce vasorelaxation. Our simulations also indicate that basal superoxide concentrations may be too low to affect medullary NO levels but that, under pathological conditions, superoxide may be a very significant scavenger of NO. We also found that although oxygen is a negligible NO scavenger, medullary hypoxia may significantly enhance NO concentration gradients along the corticomedullary axis.
Zhang
Wensheng
W
Department of Chemical and Biological Engineering, Tufts University, 4 Colby St., Medford, MA 02155, USA. wensheng.zhang@tufts.edu
Pibulsonggram
Tosapol
T
Edwards
Aurélie
A
D000818:Animals; D001692:Biological Transport; D002463:Cell Membrane Permeability; D004912:Erythrocytes / Q000378:metabolism; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D000860:Hypoxia / Q000378:metabolism; D007679:Kidney Medulla / Q000098:blood supply* / Q000378:metabolism; D007700:Kinetics; D008433:Mathematics; D008833:Microcirculation / Q000737:chemistry* / Q000378:metabolism; D008954:Models, Biological; D009569:Nitric Oxide / Q000032:analysis* / Q000096:biosynthesis / Q000097:blood*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D013481:Superoxides / Q000032:analysis / Q000097:blood
D006454:Hemoglobins; D013481:Superoxides; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase