Cardiac norepinephrine transporter protein expression is inversely correlated to chamber norepinephrine content

Abstract

The cardiac neuronal norepinephrine (NE) transporter (NET) in sympathetic neurons is responsible for uptake of released NE from the neuroeffector junction. The purpose of this study was to assess the chamber distribution of cardiac NET protein measured using [(3)H]nisoxetine binding in rat heart membranes and to correlate NE content to NET amount. In whole mounts of atria, NET was colocalized in nerve fibers with tyrosine hydroxylase (TH) immunoreactivity. NE content expressed as micrograms NE per gram tissue was lowest in the ventricles; however, NET binding was significantly higher in the left ventricle than the right ventricle and atria (P < 0.05), resulting in a significant negative correlation (r(2) = 0.922; P < 0.05) of NET to NE content. The neurotoxin 6-hydroxydopamine, an NET substrate, reduced NE content more in the ventricles than the atria, demonstrating functional significance of high ventricular NET binding. In summary, there is a ventricular predominance of NET binding that corresponds to a high NE reuptake capacity in the ventricles, yet negatively correlates to tissue NE content.

Expressions of cardiac sympathetic norepinephrine transporter and β1-adrenergic receptor decreased in aged rats

“…But the distribution of NET proteins localized along the fibers in the myocardium may not be consistent with the TH positive fiber density. Recently, Wehrwein et al(2008) reported that the NET protein is colocalized in nerve fibers with TH immunoreactivity in murine atria; however, the NET protein does not correlate with innervation density of murine heart after normalizing to the total protein content of each of the chambers. Rather, NET appears to be equally distributed throughout the myocardium; the total NET protein was highest in the ventricles and lowest in the atria (Wright et al, 2006;Wehrwein et al, 2008).…”

“…Recently, Wehrwein et al(2008) reported that the NET protein is colocalized in nerve fibers with TH immunoreactivity in murine atria; however, the NET protein does not correlate with innervation density of murine heart after normalizing to the total protein content of each of the chambers. Rather, NET appears to be equally distributed throughout the myocardium; the total NET protein was highest in the ventricles and lowest in the atria (Wright et al, 2006;Wehrwein et al, 2008). In contrast, postsynaptic effector, β-AR, is uniformly distributed throughout the myocardium, with similar densities in both atrial and ventricular tissues (Hata et al, 2004).…”

“…Since NET is a component of sympathetic nerves, the recent report by Bruzzone et al(2003) of an age-related decrease of the sympathetic is consistent with the present finding of a lower NET density with age. The reduction in NET protein might also be at least partly due to a loss of the nerve terminals, even though the NET protein does not correlate with the innervation density in myocardium (Wright et al, 2006;Wehrwein et al, 2008). The finding suggests that the upstream modulator of β-AR, cardiac symapthetic NET, may have a predominant role in age-related density downregulation of myocardial β 1 -AR in senescent rats, which may contribute to both of β-AR downregulation and age-related decrease of cardiac β-adrenergic responsiveness.…”

Regional changes in cardiac and stellate ganglion norepinephrine transporter in DOCA–salt hypertension

“…Thus, the reduction of heart NE reuptake is not due to a global reduction in cardiac NET protein expression and there is regional regulation of NET protein. There is a low amount of NET in the atria compared to the ventricles (Wehrwein et al, 2008) and the ventricles have greater uptake capacity compared to the atria so it is unlikely that a reduction in left atrium NET protein in hypertension would be enough to result in a reduction in whole heart uptake. Having ruled out a loss of NET protein in the heart as a cause for reduced reuptake, other factors that could cause a decrease in NE uptake must be considered.…”

Expression and Distribution of Dopamine Transporter in Cardiac Tissues of the Guinea Pig

“…Numerous studies have demonstrated the presence of different components of cholinergic and sympathetic neurotransmission markers as choline and noradrenaline transporters that support the presence of cholinergic and sympathetic nerve cells into the heart [22][23][24][25][26]. Also it has been reported the presence of different neural markers, that suggest the presence of histaminergic, nitrergic, peptidergic, and serotonergic neurotransmission in the same organ [27][28][29].…”