Hypertension is associated with noradrenergic hyperactivity and oxidative stress(1). We hypothesized that Ca2+ signalling in postganglionic sympathetic neurons is enhanced in spontaneously hypertensive rats (SHR). To test this, we measured depolarisation (high [K+]0) evoked Ca2+ influx in sympathetic neurons from hypertensive and normotensive Wistar-Kyoto (WKY) rats. Rats were humanely killed by an approved Home Office schedule 1 method. Superior cervical ganglia (SCG) were enzymatically isolated from age and gender matched SHR and WKY rats and plated onto poly-D-lysine/ laminin coated 6 mm cover slips and cultured 2-3 days in N2 medium(2). Intracellular Ca2+ concentration ([Ca2+]i) was measured with ratio imaging using fura-2(3). Neurons were briefly perfused with Tyrode’s solution containing 100 mM KCl to induce membrane depolarization, and the resultant transient increase in [Ca2+]i was determined. In neonatal (4-7 days) rats, [Ca2+]i transients were significantly higher in the SHR (2.65 ±0.11 µM, n=14) compared with the WKY rats (1.88 ± 0.12 µM, n=9, p<0.001, unpaired t-test). In young pre-hypertensive (4-5 weeks) rats, [Ca2+]i transients were higher in the SHR (male: 2.51 ± 0.34 µM, n=14; female: 1.98 ± 0.13 µM, n=23) compared with the gender matched WKY rats (male: 1.81 ± 0.30 µM, n=14, p<0.05, unpaired t-test; female: 1.66 ± 0.10 µM, n=24, p=0.07). In adult (16-18 weeks) rats the [Ca2+]i transients were also significantly increased in the SHR (male: 3.70 ± 0.21 µM, n=11; female: 2.93 ± 0.22 µM, n=13) compared with the gender matched adult WKY rats (male: 2.46 ± 0.17 µM, n=11, p<0.01, unpaired t-test; female: 1.83 ± 0.14µM, n=19, p<0.001, unpaired t-test). Interestingly, there were no gender differences in young SHR and WKY rats, whereas in adult SHR and WKY, [Ca2+]i transients were significantly higher in male than female (both p<0.05, unpaired t-test). These results demonstrate that increased Ca2+ transients were observed in postganglionic sympathetic neurons from newborn pre-hypertensive SHR when compared with the WKY. The overall responses are consistent with the hypothesis that enhanced Ca2+ signalling may contribute to the noradrenergic hyperactivity that precedes hypertension itself.