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Hypertension. 2002;39:293-297
doi: 10.1161/hy0202.104137
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(Hypertension. 2002;39:293.)
© 2002 American Heart Association, Inc.


Scientific Contributions

Nitric Oxide Blockade Enhances Renal Responses to Superoxide Dismutase Inhibition in Dogs

Dewan S.A. Majid; Akira Nishiyama

From the Department of Physiology, Tulane University Health Sciences Center, 1430 Tulane Ave, New Orleans, La 70112. Present address for Akira Nishiyama is Department of Pharmacology, Kagawa Medical University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan.

Correspondence to Dr Dewan S.A. Majid, Department of Physiology, SL 39, Tulane University Health Sciences Center, 1430 Tulane Ave, New Orleans, LA 70112. E-mail majid{at}tulane.edu

To examine the potential role of superoxide anion (O2-) and its interaction with NO in the regulation of renal hemodynamics and excretory function, we have evaluated the renal responses to enhancement in O2- activity before and during NO synthase inhibition in anesthetized dogs (n=6). Intraarterial infusion of a superoxide dismutase (SOD) inhibitor, diethyldithiocarbamate (DETC; 0.1 and 0.5 mg/kg per min) was made to enhance O2- activity in the kidney. Cortical (CBF), medullary (MBF), and total renal blood flow (RBF) responses were assessed using laser-Doppler needle flow probes and an electromagnetic flow probe. DETC caused dose-dependent changes in renal parameters, which were recovered within 30 minutes after the termination of DETC infusion. The high-dose infusion of DETC for 25 minutes resulted in an increase of 29±10% in renal vascular resistance (control, 35.4±4.4 mm Hg/mL per min per g) and decreases of 21±5% in RBF (control, 3.5±0.5 mL/min per g), 20±5% in CBF, 21±7% in MBF, 62±11% in urine flow (control, 10.5±2.2 µL/min per g), and 47±11% in sodium excretion (control, 2.1±0.2 µmol/min per g), without a significant change (-10±6%) in glomerular filtration rate (control, 0.74±0.09 mL/min per g). During NO synthase inhibition with intraarterial administration of nitro-L-arginine (50 µg/kg per min), the same dose of DETC showed a greater increase in renal vascular resistance (73±15%) and reductions in RBF (39±4%), CBF (32±5%), MBF (34±6%), urine flow (78±5%), and sodium excretion (67±10%), with a marked reduction in glomerular filtration rate (59±7%). These data indicate that O2- exerts renal vasoconstriction as well as antidiuretic and antinatriuretic effects. These responses are enhanced during NO synthase blockade, suggesting that NO serves a renoprotective effect against these action of O2-.


Key Words: renal hemodynamics • renal regional blood flow • sodium excretion • diethyldithiocarbamate




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