Respiratory modulated sympathetic activity: a putative mechanism for developing vascular resistance?

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 noradrenaline reuptake.

Systemic leukotriene B4 receptor antagonism lowers arterial blood pressure and improves autonomic function in the spontaneously hypertensive rat

“…; Briant et al . ). Notably, the timing of this fall in arterial pressure also coincided with the effects of CP‐105,696 on reducing the levels of circulating CD11b + expression after 5 days.…”

“…Mechanistically, these data are suggestive of a possible decline in vasomotor sympathetic activity occurring at the time when blood pressure became reduced. Interestingly, the reduction in HF(SBP) was most pronounced and indicates a reduction in either the mechanical effect of respiration on SBP, which may be associated with the reduction in respiration rate seen in the SHR-CP-105,696 group, or reduced respiratory modulation of sympathetic activity, which significantly contributes to vasomotor tone in the SHR (Simms et al 2009;Moraes et al 2014;Briant et al 2015). Notably, the timing of this fall in arterial pressure also coincided with the effects of CP-105,696 on reducing the levels of circulating CD11b + expression after 5 days.…”

Acute effects of resonance frequency breathing on cardiovascular regulation

“…Hence, the sympatho‐inhibition observed during either RF or RF + 1 seems to occur as a result of changes in the bursting pattern of MSNA imposed by the ability of the respiration to modulate the timing of bursts. Such changes are potentially critical because the respiratory‐modulated bursting of sympathetic activity has been shown to modulate vascular resistance (Briant, O'Callaghan, Champneys, & Paton, ).…”

Changes in the inspiratory pattern contribute to modulate the sympathetic activity in sino‐aortic denervated rats

“…Typically, the pattern of sympathetic activity shows a respiratory periodicity, which consists of an increase in sympathetic activity during inspiration and a reduction during expiratory phases (E-1 and E-2; Zoccal et al 2008;Costa et al 2013;Souza et al 2016), indicating a coupling between the respiratory and the sympathetic neural circuits. The interaction between respiratory and sympathetic networks is different in each experimental model of neurogenic hypertension, resulting in sympathetic overactivity in different phases of the respiratory cycle (Czyżyk-Krzeska & Trzebski, 1990;Zoccal et al 2008;Simms et al 2009;Toney et al 2010;Briant et al 2015;Souza et al 2016). In the present study, the levels of sympathetic outflow during the three respiratory phases of the respiratory cycle were normal in SAD compared with Sham rats.…”