Evaluation of the cardiovascular actions of sympathetic ganglion endothelin B receptors

Endothelin B receptors (ET B R) are found on blood vessels, renal tubules and sympathetic neurons and are upregulated in hypertensive celiac ganglion (CG). Chronic activation of ET B R with the selective agonist sarafotoxin 6c (S6c) causes hypertension that is attenuated in rats with celiac ganglionectomy (CGX). Thus S6c may increase blood pressure (BP) by activating ET B R on both blood vessels and CG. We evaluated the importance of ganglionic ET B R using two transgenic (TG) strains of rats: TG(+/+) rats have the normal complement of wild type ET B R (WT‐ET B R), whereas TG(sl/sl) rats lack functional WT‐ET B R; both strains have 70 copies of an ET B R transgene in sympathetic neurons. S6c infusion raised BP modestly in TG(+/+) rats and CGX blocked this effect. S6c‐induced hypertension was completely absent in TG(sl/sl) rats with or without CG. Thus, the ET B R transgene does not appear to be functional in sl/sl rats. We compared total (TG+WT) ET B R mRNA and protein levels in CG of the TG strains to that from WKY. ET B R mRNA levels were significantly greater in both TG strains compared to WKY (p<0.05, n=3). However, ET B R protein expression in CG was higher in WKY than in either TG strain. Thus, the presence of the ET B R transgene in ganglia appears to interfere with the expression of WT‐ET B R. We conclude that hypertension mediated by ET B R depends on the presence of WT‐ET B R in both sympathetic ganglia and vasculature. (Supported by PO1HL79687)