Published online before print December 27, 2004, doi: 10.1161/01.HYP.0000153051.56460.6a
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(Hypertension. 2005;45:283.)
© 2005 American Heart Association, Inc.
Scientific Contributions |
NADPH Oxidase Inhibition Attenuates Oxidative Stress but Not Hypertension Produced by Chronic ET-1
From the Departments of Pharmacology and Toxicology (A.A.E., J.S.P., D.M.P.) and Surgery (D.M.P.), and the Vascular Biology Center (E.D.L., J.S.P., D.M.P.), Medical College of Georgia, Augusta, Ga.
Correspondence to David M. Pollock, PhD, Vascular Biology Center, Medical College of Georgia, Augusta, GA 30912-2500. E-mail dpollock{at}mail.mcg.edu
Experiments were conducted to test the hypothesis that hypertension produced by chronic ET-1 infusion is mediated by NADPH oxidase-dependent superoxide production. Mean arterial pressure (MAP) was continuously monitored in male Sprague Dawley rats by telemetry. After baseline measurements, rats were placed on a high-salt diet (8% NaCl) and osmotic minipumps were implanted to infuse ET-1 (5 pmol/kg per minute intravenous) for 12 days. Control rats were maintained on the high-salt diet only. Separate groups of rats were also infused with ET-1 and given the superoxide dismutase mimetic, tempol (1 mmol/L), or the NADPH oxidase inhibitor, apocynin (1.5 mmol/L), in the drinking water. Infusion of ET-1 significantly increased MAP when compared with baseline values (132±3 versus 114±2 mm Hg, P<0.05). Neither tempol nor apocynin treatment had any effect on the increase in MAP produced by ET-1 when compared with baseline values (127±5 versus 113±2 and 130±3 versus 115±2 mm Hg, respectively). Plasma 8-isoprostane, an indicator of oxidative stress, was significantly increased in ET-1–infused rats compared with rats on a high-salt diet alone (128±33 versus 51±5 pg/mL; P<0.05). Both tempol and apocynin treatment significantly attenuated the ET-1–induced increase in plasma 8-isoprostane (72±10 and 61±6 pg/mL, respectively). Similarly, ET-1 infusion also significantly increased aortic superoxide production (chemiluminescence and dihydroethidium staining techniques), which was prevented by both tempol and apocynin. These data provide evidence that chronic ET-1 infusion increases vascular NADPH oxidase-dependent superoxide production but does not account for chronic ET-1–induced hypertension.
Key Words: endothelin • oxidative stress • sodium
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