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Cardiac sympathetic innervation originates in the stellate ganglia. Norepinephrine (NE) reuptake via NE transporter (NET), and release of NE from sympathetic nerve terminals are regulated by the endothelin-I (ET1) receptors, ETA and ETB, respectively. Regulation of NET by ET1 in the stellate ganglia is unknown. ETB receptor deficient rats (ETB -/-) lack functional ETB receptors in all tissues except those expressing dopamine beta hyrdoxylase (DBH). Since functional ETB expression is coupled to DBH promoter (DBH-ETB) in this model, it is possible that sympathetic neurons overexpress ETB. The purpose of this study was to examine ETB and NET in the stellate ganglia of ETB -/- rats using histology and PCR. Histology revealed that there was a significant elevation of ETB receptor protein in both the nuclear (n=4, p<0.0001) and cytoplasmic compartments (n=4, p<0.0001) in bilateral stellate ganglia from ETB -/- rats. In all stellate ganglion neurons from ETB -/- rats, NET protein was significantly increased (n=3, p<0.05), while NET mRNA was unchanged (n=3-6, p>0.05), suggesting that ET1 modulation of NET is post-transcriptional. In summary, the ETB -/- rat overexpresses ETB and NET protein in the stellate ganglia revealing an important feature of this animal model that is otherwise devoid of functional ETB receptors. This supports the notion that altered ET1 signaling can regulate NET in ganglia. [ABSTRACT FROM AUTHOR]