Role of Nitric Oxide in the Control of Renal Oxygen Consumption and the Regulation of Chemical Work in the Kidney

From the Department of Physiology (S.K.L., T.V., P.R.F., J.T., X.X., M.O., C.I.T., T.H.H.) and the Department of Pharmacology (A.N.), New York Medical College, Valhalla, NY.

Correspondence to Thomas H. Hintze, PhD, Department of Physiology, New York Medical College, Valhalla, NY 10595. E-mail Thomas_Hintze{at}nymc.edu

Abstract—Inhibition of NO synthesis has recently been shown to increase oxygen extraction in vivo, and NO has been proposed to play a significant role in the regulation of oxygen consumption by both skeletal and cardiac muscle in vivo and in vitro. It was our aim to determine whether NO also has such a role in the kidney, a tissue with a relatively low basal oxygen extraction. In chronically instrumented conscious dogs, administration of an inhibitor of NO synthase, nitro-L-arginine (NLA, 30 mg/kg IV), caused a maintained increase in mean arterial pressure and renal vascular resistance and a decrease in heart rate (all P<0.05). At 60 minutes, urine flow rate and glomerular flow rate decreased by 44±12% and 45±7%, respectively; moreover, the amount of sodium reabsorbed fell from 16±1.7 to 8.5±1.1 mmol/min (all P<0.05). At this time, oxygen uptake and extraction increased markedly by 115±37% and 102±34%, respectively (P<0.05). Oxygen consumption also significantly increased from 4.5±0.6 to 7.1±0.9 mL O₂/min. Most important, the ratio of oxygen consumption to sodium reabsorbed increased dramatically from 0.33±0.07 to 0.75±0.11 mL O₂/mmol Na⁺ (P<0.05), suggesting a reduction in renal efficiency for transporting sodium. In vitro, both a NO-donating agent and the NO synthase–stimulating agonist bradykinin significantly decreased both cortical and medullary renal oxygen consumption. In conclusion, NO plays a role in maintaining a balance between oxygen consumption and sodium reabsorption, the major ATP-consuming process in the kidney, in conscious dogs, and NO can inhibit mitochondrial oxygen consumption in canine renal slices in vitro.

Key Words: nitro-L-arginine • Na⁺ reabsorption • nitrate/nitrite • renal slice

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