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

Activation of ETB receptors increases superoxide levels in sympathetic ganglia in vivo. Am J Physiol Regul Integr Comp Physiol 290: R90 - R95, 2006. First published September 22, 2005; doi: 10.1152/ajpregu. 00505.2005. - Dai and colleagues ( Dai X, Galligan JJ, Watts SW, Fink GD, and Kreulen DL. Hypertension 43: 1048 - 1054, 2004) found that endothelin (ET) stimulated O-2(-) production in sympathetic ganglion neurons in vitro by activating ETB receptors. The objective of the present study was to determine whether activation of ETB receptors in vivo elevates O-2(-) levels in sympathetic ganglia. Because ETB receptor activation increases blood pressure, we also sought to determine whether alteration in O-2(-) levels was a direct effect of ETB receptor activation on sympathetic ganglia or an indirect consequence of hypertension. Male Sprague-Dawley rats received intravenous infusions of either the specific ETB 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 O-2(-) 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 O-2(-) production, a separate group of rats received phenylephrine (PE; 10 mu g (.) 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 ETB receptor activation in vivo significantly enhances O-2(-) levels in sympathetic ganglia, due to both pressor effects and direct stimulation of ETB receptors in ganglion cells.