The adult spontaneously hypertensive rat (SHR) has increased peripheral cardiac sympathetic activity compared to Wistar Kyoto (WKY) controls. Recent studies in 4 week old pre-hypertensive SHRs have also shown increased calcium transients1, and a reduction in NET activity2 in isolated stellate ganglion neurons compared to age matched WKYs. The functional significance of these changes in terms of NE release and change in heart rate during sympathetic stimulation is unknown. We therefore hyposthesised that peripheral sympathetic responsiveness in the SHR at 4 weeks of age would be exaggerated compared to the WKY. Ventricular weight/body weight ratios (WKY: n=7, SHR: n=8) and mean arterial pressure (WKY: n=20, SHR: n=19) measured via the left carotid artery (under 2% isoflurane) demonstrated that SHRs were without left ventricular hypertrophy and were normotensive at this age compared to WKYs. However, a small but significant (p<0.05, unpaired student t-¬test) tachycardia is observed in the young SHR in vivo (WKY: 298±11 bpm, n=20 vs. SHR: 335±8 bpm, n=19) although the heart rate response to vagus nerve stimulation (3Hz and 5Hz, 30sec, 20V, 1msec) is unchanged compared to the WKY (WKY, n=10, SHR, n=12). In an isolated organ bath atrial preparation with intact right stellate ganglion (37±0.5oC) there was a greater heart rate response to stellate stimulation (5 and 7Hz, 30sec, 20V, 1msec) in SHRs compared to WKYs (SHR, n=9, WKY, n=7). There was also a significantly greater release of 3H-NE to field stimulation (5Hz, 20V, 1msec) of right atria (n=7 for both groups) and higher plasma levels of the sympathetic co-transmitter neuropeptide Y sampled from the right atria (measured with ELISA, n=12 for both groups). The difference in 3H-NE release between the young SHR and WKY could be normalized by the NET inhibitor desipramine (1μM, SHR n=10, WKY n=8) but not the α2 receptor antagonist yohimbine (1μM, SHR n=7, WKY n=8). Increased cardiac sympathetic neurotransmission driven by a larger neuronal calcium transient and reduced NE reuptake may therefore represent an early marker in the development of hypertension and contribute to a resting tachycardia in vivo. Keywords: Spontaneously hypertensive rat, cardiac, autonomic neurotransmission, sympathetic, vagal, hypertension.