Increased O2*- production and upregulation of ETB receptors by sympathetic neurons in DOCA-salt hypertensive rats.
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 ET(B) 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 ET(B) receptors, but not ET(A) 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 ET(B) receptor levels in ganglia from sham and DOCA-salt animals. ET(B) receptor mRNA levels were 32% higher and ET(B) 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 ET(B) receptors.
Dai
Xiaoling
X
Department of Physiology, Michigan State University, East Lansing, MI 48823, USA.
Galligan
James J
JJ
Watts
Stephanie W
SW
Fink
Gregory D
GD
Kreulen
David L
DL
D000818:Animals; D003900:Desoxycorticosterone / Q000633:toxicity; D065130:Endothelin A Receptor Antagonists; D019332:Endothelin-1 / Q000819:agonists / Q000502:physiology*; D005728:Ganglia, Sympathetic / Q000187:drug effects* / Q000502:physiology; D006973:Hypertension / Q000139:chemically induced; D008297:Male; D020932:Nerve Growth Factor / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D016716:PC12 Cells / Q000187:drug effects / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D044023:Receptor, Endothelin B / Q000819:agonists / Q000096:biosynthesis* / Q000235:genetics; D017673:Sodium Chloride, Dietary / Q000633:toxicity; D013481:Superoxides / Q000378:metabolism*; D017779:Sympathetic Fibers, Postganglionic / Q000187:drug effects / Q000502:physiology; D015854:Up-Regulation / Q000187:drug effects; D014757:Viper Venoms / Q000494:pharmacology
D065130:Endothelin A Receptor Antagonists; D019332:Endothelin-1; D009842:Oligopeptides; D010880:Piperidines; D017382:Reactive Oxygen Species; D044023:Receptor, Endothelin B; D017673:Sodium Chloride, Dietary; D014757:Viper Venoms; C057354:sarafotoxins s6; D013481:Superoxides; C087220:BQ 610; D003900:Desoxycorticosterone; C086539:BQ 788; D020932:Nerve Growth Factor