Natriuretic peptides (NPs) have recently been reported to elicit calcium dependent noradrenaline exocytosis from PC12 cells (sympathetic neuron phenotype) via a particulate guanylyl cyclase -cGMP-PKG-mediated inhibition of PDE3-induced hydrolysis of cAMP(1). However, others have shown that the nitric oxide coupled soluble guanylyl cyclase -cGMP pathway can inhibit cardiac noradrenaline release(2). Therefore we re-visited the effect of natriuretic peptides on depolarization evoked calcium influx in cardiac sympathetic neurons in an attempt to resolve this discrepancy. 4-5 week old SD rats were humanely killed by an approved Home Office schedule 1 method, and neurons from the stellate ganglia were enzymatically isolated. Intracellular free Ca2+ concentration ([Ca2+]i) was measured by ratiometric fluorescence imaging using fura-2/AM in neurons(3). Western blot analysis was used to demonstrate NP receptor type A and B protein expression. The evoked [Ca2+]i transient was evaluated by 30 sec exposure to 50 mM KCl in the Tyrode solution. Fura-2/AM was excited alternately at 350 nm and 380 nm and the emitted fluorescence measured at 510 nm. Brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP) were tested in this study. BNP and CNP significantly reduced the depolarization evoked [Ca2+]i transient (100 nM BNP: -12.73 ± 2.80 %, n=18, P<0.01; 250 nM BNP: -21.22 ± 7.46 %, n=11, P<0.05; 100 nM CNP: -16.09 ± 4.19 %, n=6, P<0.01) in cardiac sympathetic neurons. The cell-permeable cGMP analogue, 8-Bromoguanosine 3′,5′-cyclic monophosphate (8-Br-cGMP, 100 µM), also significantly decreased the [Ca2+]i transient (-14.71 ± 5.78 %, n=13, P<0.05). In contrast to the results of Chan et al., we show that BNP and CNP reduce cardiac sympathetic Ca2+ transients, an effect mimicked by increasing intracellular cGMP.