Nitric oxide and superoxide in the renal medulla: a delicate balancing act.
OBJECTIVE
Endothelial nitric oxide synthase (eNOS) and nicotinamide adenine dinucleotide (phosphate) oxidase [NAD(P)H oxidase] are both expressed in tubular epithelial cells within the renal medulla, particularly the thick ascending limb of the loop of Henle (mTALH). Thick ascending limbs contribute to long-term blood pressure control, both because they reabsorb approximately 30% of filtered sodium, and because they produce paracrine factors like nitric oxide (NO) that control medullary blood flow (MBF), which in turn has a major impact on tubular sodium reabsorption. Herein, we review recent evidence for roles of NO and superoxide (O2*-) in autocrine control of tubular sodium reabsorption, and in paracrine control of MBF.


RESULTS
O2*- can have a direct action to reduce MBF, and to enhance sodium reabsorption from mTALH. These actions oppose those of NO produced in mTALH, which inhibits tubular sodium reabsorption (autocrine) and increases MBF (paracrine). NO and O2*- also oppose each other's actions through chemical combination to produce peroxynitrite. Thus, interactions between NO and O2*-, at both the chemical and cellular levels, likely contribute to long-term blood pressure control. This hypothesis is supported by recent data showing that sodium retention and hypertension can develop when the balance of production of these free radicals is tipped towards O2*-, such as in diabetes, atherosclerosis and renin-angiotensin-system activation.


CONCLUSIONS
Interactions between O2*- and NO produced within the mTALH regulate tubular and vascular function in the renal medulla. Dysregulation of these systems in states of oxidative stress likely promotes salt and water retention, and thus hypertension.
Evans
Roger G
RG
Department of Physiology, Monash University, Melbourne, Victoria 3800, Australia. Roger.evans@med.monash.edu.au
Fitzgerald
Sharyn M
SM
D006801:Humans; D007679:Kidney Medulla / Q000098:blood supply / Q000378:metabolism*; D008138:Loop of Henle / Q000378:metabolism; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D019255:NADPH Oxidases; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D017382:Reactive Oxygen Species / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism*
D017382:Reactive Oxygen Species; D013481:Superoxides; D009569:Nitric Oxide; D012964:Sodium; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D009247:NADH, NADPH Oxidoreductases; D019255:NADPH Oxidases