Activation of ETB receptors increases superoxide levels in sympathetic ganglia in vivo.
Dai and colleagues (Dai X, Galligan JJ, Watts SW, Fink GD, and Kreulen DL. Hypertension 43: 1048-1054, 2004) found that endothelin (ET) stimulated O2- production in sympathetic ganglion neurons in vitro by activating ET(B) receptors. The objective of the present study was to determine whether activation of ET(B) receptors in vivo elevates O2- levels in sympathetic ganglia. Because ET(B) receptor activation increases blood pressure, we also sought to determine whether alteration in O2- levels was a direct effect of ET(B) receptor activation on sympathetic ganglia or an indirect consequence of hypertension. Male Sprague-Dawley rats received intravenous infusions of either the specific ET(B) receptor agonist sarafotoxin 6c (S6c; 5 pmol.kg(-1).min(-1)) or isotonic saline at 0.01 ml/min (control) for 120 min. To measure O2- levels, we removed the inferior mesenteric ganglion immediately after infusion and stained it with dihydroethidine (DHE). Mean arterial pressure increased 26.6 +/- 1.7 mmHg in the S6c-treated rats and 3.65 +/- 6 mmHg in control rats. Measurements of average pixel intensity revealed that the DHE fluorescence in ganglionic neurons and surrounding glial cells were 96.7% and 160% greater in S6c-treated than in control rats, respectively. To evaluate the effect of elevated blood pressure on O2- production, a separate group of rats received phenylephrine (PE; 10 mug.kg(-1).min(-1) iv) for 2 h. MAP increased 31 +/- 1.2 mmHg in PE-infused rats. The DHE fluorescence intensity in ganglia of PE-infused rats was significantly greater than that of control rats, 137.7% in neurons and 104.6% in glia but significantly lower than in ganglia from S6c rats. We conclude that ET(B) receptor activation in vivo significantly enhances O2- levels in sympathetic ganglia, due to both pressor effects and direct stimulation of ET(B) receptors in ganglion cells.
Lau
Yanny E
YE
Department of Pharmacology/Toxicology, B327 Life Science, Michigan State University, East Lansing, MI 48824, USA.
Galligan
James J
JJ
Kreulen
David L
DL
Fink
Gregory D
GD
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D019332:Endothelin-1 / Q000378:metabolism; D005728:Ganglia, Sympathetic / Q000378:metabolism*; D008297:Male; D010656:Phenylephrine; D051381:Rats; D017207:Rats, Sprague-Dawley; D044022:Receptor, Endothelin A / Q000378:metabolism; D044023:Receptor, Endothelin B / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism*; D014757:Viper Venoms
D019332:Endothelin-1; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D014757:Viper Venoms; C057354:sarafotoxins s6; D013481:Superoxides; D010656:Phenylephrine