Hypertension is associated with an increase in cardiac sympathetic transmission, although the exact mechanism underlying this is unknown. Enhanced intracellular calcium transients and cardiac norepinephrine (NE) release have been reported in pre-hypertensive and hypertensive spontaneously hypertensive rats (SHR) compared to normotensive controls (WKY: Wistar-Kyoto). This neural phenotype might also result from defective NET-1 transport (uptake-1). The dynamic kinetics of NET were monitored temporally using a novel fluorescent assay (NTUA) of the transporter in cultured postganglionic sympathetic neurons from the cardiac stellate ganglion, the superior cervical ganglion, the celiac ganglia/superior mesenteric ganglia, and the renal sympathetic chain. All NET activity was blocked by desipramine. NET rate was significantly impaired in stellate sympathetic neurons from the pre-hypertensive SHR compared to age matched normotensive WKY (4 week SHR, n=24, WKY, n=21, P<0.05, unpaired t test). A similar response was seen in hypertensive SHR cardiac sympathetic neurons (16 week SHR, n=20, WKY, n=19, P<0.05, unpaired t test). However, no reduction in transporter rate was observed at either age in the other major non-cardiac sympathetic ganglia. NET is modulated by receptor coupled pathways. In particular brain naturitic peptide (BNP) plasma levels are dramatically increased during cardiac stretch, volume overload and left ventricular dysfunction. Interestingly they have also been linked to regulating cardiac sympathetic neurotransmission since BNP reduces intracellular calcium transients and transmitter release. We found BNP significantly reduced the NET transporter in the WKY (S1/S2 ratio control, n=18, BNP 250nM, n=25, P<0.0001, unpaired t test). Taken together this could allow NE to stay at appropriate levels in the synapse. Whether this pathway is dysregulated in the SHR remains to be determined. Key words: Cardiac, Sympathetic, Hypertension, Spontaneously hypertensive rat, norepinephrine re-uptake transporter.