Journal article
Oxygen-Derived Free Radicals Contribute to Baroreceptor Dysfunction in Atherosclerotic Rabbits
Circulation research, Vol.79(4), pp.802-811
10/1996
DOI: 10.1161/01.RES.79.4.802
PMID: 8831504
Abstract
The goal of the present study was to determine whether oxygen-derived free radicals contribute to baroreceptor dysfunction in atherosclerosis. Baroreceptor activity was measured from the carotid sinus nerve during pressure ramps in isolated carotid sinuses of anesthetized rabbits. Rabbits fed a 0.5% to 1.0% cholesterol diet for 7.9 +/- 0.4 months (mean +/- SE; range, 5.5 to 10) developed atherosclerotic lesions in the carotid sinuses. Maximum baroreceptor activity measured at 140 mm Hg and the slope of the pressure-activity curve were reduced in atherosclerotic (n = 15) compared with normal (n = 13) rabbits (425 +/- 34 versus 721 +/- 30 spikes per second and 6.2 +/- 0.6 versus 10.8 +/- 0.8 spikes per second per mm Hg, respectively, P < .05). The level of activity was inversely related to plasma cholesterol concentration (r = .86, P < .001) and total cholesterol load (plasma concentration x duration of diet, r = .92). Mean arterial pressure was normal in both groups. Exposure of the carotid sinus to the free-radical scavengers superoxide dismutase (SOD) and catalase significantly increased maximum baroreceptor activity by 25 +/- 4% in atherosclerotic rabbits (n = 6) but caused only small and irreversible changes in activity in normal rabbits (n = 8). Catalase alone but not SOD also increased baroreceptor activity in atherosclerotic rabbits (n = 7). Exposure of the carotid sinus of normal rabbits to exogenous free radicals generated from the reaction between xanthine and xanthine oxidase inhibited baroreceptor activity in a dose-dependent and reversible manner (n = 8, P < .05). The inhibition of activity was attenuated by SOD and catalase but was not attenuated by the inhibitor of hydroxyl radical formation, deferoxamine. Neither restoration of baroreceptor activity in atherosclerotic rabbits by catalase nor inhibition of activity by xanthine/xanthine oxidase could be explained by changes in the carotid pressure-diameter relation or prostacyclin formation. These results indicate that oxidant stress inhibits baroreceptor activity and that endogenous oxyradicals produced in atherosclerotic carotid sinuses contribute to baroreceptor dysfunction.
Details
- Title: Subtitle
- Oxygen-Derived Free Radicals Contribute to Baroreceptor Dysfunction in Atherosclerotic Rabbits
- Creators
- Zhi Li - University of IowaHui Z Mao - the Cardiovascular Center and the Departments of Internal Medicine (Z.L., H.Z.M., F.M.A., M.W.C.) and of Physiology and Biophysics (F.M.A.), University of Iowa College of Medicine, and the Department of Veterans Affairs Medical Center (M.W.C.), Iowa City, IowaFrancois M Abboud - the Cardiovascular Center and the Departments of Internal Medicine (Z.L., H.Z.M., F.M.A., M.W.C.) and of Physiology and Biophysics (F.M.A.), University of Iowa College of Medicine, and the Department of Veterans Affairs Medical Center (M.W.C.), Iowa City, IowaMark W Chapleau - the Cardiovascular Center and the Departments of Internal Medicine (Z.L., H.Z.M., F.M.A., M.W.C.) and of Physiology and Biophysics (F.M.A.), University of Iowa College of Medicine, and the Department of Veterans Affairs Medical Center (M.W.C.), Iowa City, Iowa
- Resource Type
- Journal article
- Publication Details
- Circulation research, Vol.79(4), pp.802-811
- DOI
- 10.1161/01.RES.79.4.802
- PMID
- 8831504
- ISSN
- 0009-7330
- eISSN
- 1524-4571
- Language
- English
- Date published
- 10/1996
- Academic Unit
- Molecular Physiology and Biophysics; Cardiovascular Medicine; Fraternal Order of Eagles Diabetes Research Center; Internal Medicine
- Record Identifier
- 9984025696502771
Metrics
20 Record Views