Sympathetic nerve activity (SNA) exhibits respiratory modulation. This component of SNA is important ‐ being recruited under cardiorespiratory reflex conditions and elevated in the spontaneously hypertensive (SH) rat – and yet, the exact influence of this modulation on vascular tone is not understood, even in normotensive conditions. We constructed a mathematical model of the sympathetic innervation of an arteriole, and used it to test the hypothesis that respiratory modulation of SNA preferentially increases vasoconstriction compared to a frequency‐matched tonic pattern. Simulations supported the hypothesis, where respiratory modulated increases in vasoconstriction were mediated by a noradrenergic mechanism. These predictions were tested in vivo in adult Wistar rats. Stimulation of the sympathetic chain (L3) with respiratory‐modulated bursting patterns, revealed that bursting increases vascular resistance (VR) more than tonic stimulation (57.8 ± 3.3% vs 44.8 ± 4.2%; P < 0.001; n = 8). The onset of the VR response was also quicker for bursting stimulation (rise time‐constant = 1.98 ± 0.09 s vs 2.35 ± 0.20 s; P < 0.01). In adult SH rats (n = 8), the VR response to bursting (44.6 ± 3.9%) was not different to tonic (37.4 ± 3.5%; P = 0.57). Using both mathematical modelling and in vivo techniques, we have shown that VR depends critically on respiratory modulation and revealed that this pattern‐dependency in Wistar rats is due to a noradrenergic mechanism. This respiratory component may therefore contribute to the ontogenesis of hypertension in the pre‐hypertensive SH rat ‐ raising VR and driving vascular remodelling. Why adult SH rats do not exhibit a pattern‐dependent response is not known, but further modelling revealed that this may be due to dysfunctional NA reuptake. This article is protected by copyright. All rights reserved