Novel localization of norepinephrine transporter in sensory nerve endings in heart

Abstract

The cardiac neuronal norepinephrine transporter (NET) is responsible for uptake of NE from the neuroeffector junction. There is ample evidence of reduced function of NET in hypertension, heart failure, and orthostatic intolerance. Studies on the localization of cardiac NET are limited, and suggest that NET is found in sympathetic fibers and intrinsic cardiac adrenergic cells. We hypothesized that NET would also be present in sensory terminals that innervate the heart. Histology and RT-PCR were used. Fixed atria and mesenteric vessels from normal, adult rats were stained for tyrosine hyrdoxylase (TH) and NET to confirm localization of NET to cardiac sympathetic nerve fibers (n=1). NET and TH were colocalized in the majority of fibers. However, there are NET-positive fibers that were TH-negative and presumably non-sympathetic. In these nerve fibers NET colocalized with calcitonin gene related peptide (CGRP), a marker of sensory neurons (n=1). The pattern of NET staining was the same in mesenteric blood vessels (n=1), suggesting that NET and CGRP colocalization is not unique to the heart. Dorsal root ganglion cell bodies, which receive sensory afferents from heart and mesentery, are positive for NET protein and express NET mRNA (n=4). In conclusion, sensory neurons are a source of NET in the heart that should be considered when assessing dysfunction of cardiac NET in disease. This is the first report of NET mRNA and protein in cardiac sensory nerves. Funding: AHA predoctoral fellowship and PO1HL70687.