Abstract
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.
Original language | English |
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Pages (from-to) | 5341–5360 |
Number of pages | 20 |
Journal | Journal of Physiology |
Volume | 593 |
Issue number | 24 |
Early online date | 28 Oct 2015 |
DOIs | |
Publication status | Published - 15 Dec 2015 |
Research Groups and Themes
- Engineering Mathematics Research Group
Keywords
- Vascular resistance
- respiratory-sympathetic coupling
- hypertension
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Professor Alan R Champneys
- School of Engineering Mathematics and Technology - Professor of Applied Non-linear Mathematics
- Cabot Institute for the Environment
- Systems Centre
Person: Academic , Member