Activation of ETB receptors increases superoxide levels in sympathetic ganglia in vivo.

Abstract

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.

• Authors: Yanny E Lau, James J Galligan, David L Kreulen, Gregory D Fink
• Journal: American journal of physiology. Regulatory, integrative and comparative physiology (Am J Physiol Regul Integr Comp Physiol) Vol. 290 Issue 1 Pg. R90-5 (Jan 2006) ISSN: 0363-6119 [Print] United States
• PMID: 16179487 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Endothelin-1
• Receptor, Endothelin A
• Receptor, Endothelin B
• Viper Venoms
• sarafotoxins s6
• Superoxides
• Phenylephrine

Topics

• Animals
• Blood Pressure (drug effects, physiology)
• Endothelin-1 (metabolism)
• Ganglia, Sympathetic (metabolism)
• Male
• Phenylephrine
• Rats
• Rats, Sprague-Dawley
• Receptor, Endothelin A (metabolism)
• Receptor, Endothelin B (metabolism)
• Superoxides (metabolism)
• Viper Venoms