Key result
6-hydroxydopamine treatment significantly depleted norepinephrine levels (p<0.001) but did not destroy cardiac sympathetic nerve fibers or alter other neuronal markers.
p-value: p=<0.001
6-hydroxydopamine depletes cardiac norepinephrine but does not destroy sympathetic nerve fibers, indicating its action is limited to NE depletion rather than complete chemical denervation.
Refines 6-OHDA mechanism in animal cardiac models; leaves open translation to clinical sympathetic modulation.
6‐hydroxydopamine (6‐OHDA) is used to “chemically denervate” tissues innervated by nerves containing catecholamine transporters. Treatment reduces the norepinephrine (NE) content of the heart but little is known about other markers of sympathetic nerves. The purpose of this study was to examine the effects of 6‐OHDA on cardiac sympathetic neurons innervating the right atrium. 6‐OHDA (250 mg/kg, sub.q, 3 doses over 7 days) was administered to adult rats and on day 7 hearts were removed. There was a significant decrease in NE levels determined by capillary electrophoresis with electrochemical detection (p<0.001, n=3) confirming that the treatment was effective. However, immunocytochemical staining showed tyrosine hydroxylase was still visible in neurons after denervation (n=3). Western blotting revealed no differences in protein expression for either the neuronal marker Protein Gene Product 9.5 (p>0.05, n=4) or for three molecular weight variants of NE transporter (NET) (80, 54, and 46 kD) in the right atria (p>0.05. n=3‐4). In addition, qPCR showed no change in the levels of mRNA for NET compared to untreated controls (p>0.05, n=6). Similar results were seen in all other heart chambers. Therefore, 6‐OHDA does not destroy cardiac sympathetic nerve fibers; its action appears limited to the depletion of NE. Support: PO1HL70687.
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Esfahanian et al. (2007) studied this question. 6-hydroxydopamine (6-OHDA) vs. untreated controls was evaluated on Norepinephrine (NE) levels (p=<0.001). 6-hydroxydopamine treatment significantly depleted norepinephrine levels (p<0.001) but did not destroy cardiac sympathetic nerve fibers or alter other neuronal markers.
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