Sympathetic nerve activity (SNA) is elevated in hypertension. The question of how the end-organ vasculature responds at a cellular and molecular level to the bursty respiratory component of SNA remains unknown, although this is believed to underlie Traube-Hering waves. Experimental studies have shown that ‘irregular’ activity generates a larger contractile force in arterial smooth muscle cells (SMCs) than tonic activity of the same average firing frequency [1]. This suggests that the respiratory modulation that SNA exhibits could be a key determinant of blood pressure, and that the change in the respiratory component could cause an increase in blood pressure, as seen in the spontaneously hypertensive rat [2]. To test this hypothesis we have constructed a high-fidelity mathematical model of the pathway of transmission from a sympathetic preganglionic neurone (SPN) to a SMC. A single-cell model of a SPN, previously presented [3], was used to drive the pathway. The presynaptic, intracellular calcium trace was used to drive a model of noradrenaline release. The released transmitter, with a profile fitted to carbon fibre electrode studies [4], activated α1-receptors on the SMC, triggering a G-protein cascade and was modelled with a 6-variable system. The subsequent release of calcium was modelled using a 2-dimensional system describing the calcium fluxes across the sarcoplasmic reticulum. These calcium dynamics were used to drive equations describing binding of myosin to actin and therefore the contractile force generated in the SMC. The resulting 25 dimensional system was run on BlueCrystal at Bristol University, using a commercial software package (MATLAB R2010a). To mimic the change in the respiratory component of SNA seen in the spontaneously hypertensive rat (SHR) versus the normotensive rat (WKY), the model was stimulated with bursts which had varying within-burst frequencies. The sympathetic inputs had the same average firing frequency of 1Hz. The simulations, shown in the figure, indicate that the respiratory component of SNA is a key determinant of blood pressure, producing a larger change in contractile force than tonic input at the same average firing frequency. Arteries have therefore adapted to the challenge of converting high-frequency output from the sympathetic nervous system, to a lower frequency contraction, and in doing so respond with some specificity to respiratory modulation. These modelling data suggests that alterations to the respiratory component need to be investigated in order to understand hypertension.