Published online before print March 29, 2004, doi: 10.1161/01.HYP.0000126068.27125.42
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(Hypertension. 2004;43:1048.)
© 2004 American Heart Association, Inc.
Scientific Contributions |
Increased O2·– Production and Upregulation of ETB Receptors by Sympathetic Neurons in DOCA-Salt Hypertensive Rats
From the Departments of Physiology (X.D., D.L.K.), Pharmacology and Toxicology (J.J.G., S.W.W., G.D.F.), and Neuroscience Program (X.D., J.J.G., G.D.F., D.L.K.), Michigan State University, East Lansing.
Correspondence to Dr David L. Kreulen, Department of Physiology, 2201 Biomedical and Physical Sciences Building, Michigan State University, East Lansing, MI 48823. E-mail dkreulen{at}msu.edu
Superoxide anion (O2·–) production is elevated in the vasculature of hypertensive animals but it is not known if O2·– production is also elevated in the sympathetic nervous system. We measured O2·– levels in prevertebral sympathetic ganglia of deoxycorticosterone acetate (DOCA)-salt hypertensive rats using the dihydroethidine (DHE) fluorescence method. O2·– was elevated in ganglia from DOCA-salt rats compared with normotensive sham rats. Treatment of ganglia with endothelin (ET)-1 (3x10–8 mol/L) resulted in a 200% increase in fluorescence intensity in neurons, which was attenuated by the ETB receptor antagonist BQ788 (10–7 mol/L). ET-1 also increased the O2·– induced fluorescence in dissociated sympathetic neurons and PC-12 cells via activation of ETB receptors, but not ETA receptors. To evaluate whether elevated ET-1 levels in the ganglia might contribute to the elevated O2·– found in ganglia we measured the amount of ET-1 using an ELISA assay. ET-1 levels in sham rat celiac ganglia were 695.6±40.9 picogram per gram; they were not different than ET-1 levels in ganglia from DOCA-salt rats. We then compared ETB receptor levels in ganglia from sham and DOCA-salt animals. ETB receptor mRNA levels were 32% higher and ETB receptor protein levels were 20% higher in celiac ganglia from DOCA-salt rats than from sham rats separately. In conclusion, O2·– is elevated in prevertebral sympathetic ganglia in DOCA-salt hypertension, and ET-1 is a potent stimulus for the elevation of O2·– levels in sympathetic ganglia, an effect that may be mediated by the upregulation of ETB receptors.
Key Words: endothelin • receptors, endothelin • hypertension • sympathetic nervous system • oxidative stress
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