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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]

Abstract: Uptake of norepinephrine via the neuronal norepinephrine transporter is reduced in the heart during deoxycorticosterone (DOCA)–salt hypertension. We hypothesized that this was due to reduced norepinephrine transporter mRNA and/or protein expression in the stellate ganglia and heart. After 4weeks of DOCA–salt treatment there was no change in norepinephrine transporter mRNA in either the right or the left stellate ganglia from hypertensive rats (n=5–7, p>0.05). Norepinephrine transporter immunoreactivity in the left stellate ganglion was significantly increased (n=4, p<0.05) while the right stellate ganglion was unchanged (n=4, p>0.05). Whole heart norepinephrine content was significantly reduced in DOCA rats consistent with reduced uptake function; however, when norepinephrine was assessed by chamber, a significant decrease was noted only in the right atrium and right ventricle (n=6, p<0.05). Cardiac norepinephrine transport binding by chamber revealed that it was only reduced in the left atrium (n=5–7, p>0.05). Therefore, 1) contrary to our hypothesis reduced reuptake in the hypertensive heart is not exclusively due to an overall reduction in norepinephrine transporter mRNA or protein in the stellate ganglion or heart, and 2) norepinephrine transporter regulation occurs regionally in the heart and stellate ganglion in the hypertensive rat heart. [Copyright &y& Elsevier]