Pharmacological assessment of the contribution of the arterial baroreflex to sympathetic discharge patterns in healthy humans

Abstract

To study how changes in baroreceptor afferent activity affect patterns of sympathetic neural activation, we manipulated arterial blood pressure with intravenous nitroprusside (NTP) and phenylephrine (PE) and measured action potential (AP) patterns with wavelet-based methodology. We hypothesized that 1) baroreflex unloading (NTP) would increase firing of low-threshold axons and recruitment of latent axons and 2) baroreflex loading (PE) would decrease firing of low-threshold axons. Heart rate (HR, ECG), arterial blood pressure (BP, brachial catheter), and muscle sympathetic nerve activity (MSNA, microneurography of peroneal nerve) were measured at baseline and during steady-state systemic, intravenous NTP (0.5-1.2 µg·kg·min, n = 13) or PE (0.2-1.0 µg·kg·min, n = 9) infusion. BP decreased and HR and integrated MSNA increased with NTP ( P < 0.01). AP incidence (326 ± 66 to 579 ± 129 APs/100 heartbeats) and AP content per integrated burst (8 ± 1 to 11 ± 2 APs/burst) increased with NTP ( P < 0.05). The firing probability of low-threshold axons increased with NTP, and recruitment of high-threshold axons was observed (22 ± 3 to 24 ± 3 max cluster number, 9 ± 1 to 11 ± 1 clusters/burst; P < 0.05). BP increased and HR and integrated MSNA decreased with PE ( P < 0.05). PE decreased AP incidence (406 ± 128 to 166 ± 42 APs/100 heartbeats) and resulted in fewer unique clusters (15 ± 2 to 9 ± 1 max cluster number, P < 0.05); components of an integrated burst (APs or clusters per burst) were not altered ( P > 0.05). These data support a hierarchical pattern of sympathetic neural activation during manipulation of baroreceptor afferent activity, with rate coding of active neurons playing the predominant role and recruitment/derecruitment of higher-threshold units occurring with steady-state hypotensive stress. NEW & NOTEWORTHY To study how changes in baroreceptor afferent activity affect patterns of sympathetic neural activation, we manipulated arterial blood pressure with intravenous nitroprusside and phenylephrine and measured sympathetic outflow with wavelet-based methodology. Baroreflex unloading increased sympathetic activity by increasing firing probability of low-threshold axons (rate coding) and recruiting new populations of high-threshold axons. Baroreflex loading decreased sympathetic activity by decreasing the firing probability of larger axons (derecruitment); however, the components of an integrated burst were unaffected.

The role of the paravertebral ganglia in human sympathetic neural discharge patterns

“…), or sodium nitroprusside infusion (Limberg et al . ), results in a paradoxical decrease in the firing of some APs including smaller clusters, supporting the notion that complex mechanisms may regulate small AP patterns.…”

Heterogeneous baroreflex control of sympathetic action potential subpopulations in humans

“…The present conclusions are based on sympathetic emissions destined for the skeletal muscle vasculature of young healthy males and females. Given replicated evidence of heterogeneous baroreflex control by AP cluster at BSL (Salmanpour & Shoemaker, 2012) and augmented AP discharge with baroreflex unloading (Salmanpour et al 2011a;Badrov et al 2015;Limberg et al 2018), we hypothesize that the observed modifications to AP baroreflex gain represent a fundamental response to orthostatic stress that may be modified by factors including hormonal variations accompanying menstrual phase (Usselman et al 2013(Usselman et al , 2015, orthostatic tolerance (Shoemaker et al 1999), and ageing/disease (Badrov et al 2016a). These findings may not be representative of the adjustments to AP baroreflex control imposed by other forms of physiological stress associated with elevated sympathetic outflow, such as physical exercise (Mueller et al 2011).…”

“…Based on preliminary observations (Salmanpour & Shoemaker, 2012;Klassen et al 2019), the hypothesis predicts that on going from BSL to LBNP, baroreflex functions for medium APs will express the greatest increase in slope and upward resetting. Also, preliminary data (Limberg et al 2018) point towards reductions in baroreflex control over the smallest APs with orthostatic stress.…”

“…Based on the observation that medium-sized AP clusters express strong baroreflex control under baseline conditions (Salmanpour & Shoemaker, 2012) we reasoned that the upward shift in baroreflex control over integrated bursts of MSNA during orthostatic stress (Ichinose et al 2004(Ichinose et al , 2006Salmanpour et al 2011a) might be related to specific control over these medium AP clusters along with relocation of the operating points to positions of greater gain to facilitate enhanced discharge. However, observations made during the hypotensive phase of a sodium nitroprusside infusion of reduced firing probability of the cluster of the smallest APs (Limberg et al 2018) suggest that this subpopulation may express reductions in baroreflex control during orthostatic stress.…”

“…However, observations made during the hypotensive phase of a sodium nitroprusside infusion of reduced firing probability of the cluster of the smallest APs (Limberg et al . 2018) suggest that this subpopulation may express reductions in baroreflex control during orthostatic stress.…”