(Hypertension. 2002;39:293.)
© 2002 American Heart Association, Inc.
Scientific Contributions |
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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