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^-1·min^-1, n = 13) or PE (0.2-1.0 µg·kg^-1·min^-1, 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.

Keywords: baroreflex; microneurography; modified Oxford technique; sympathetic outflow.

Fig. 1.

Representative sample of data from 1 subject (26 yr, 21 kg/m²) collected at baseline and during steady-state nitroprusside infusion (1.1 µg·kg⁻¹·min⁻¹). MBP, mean blood pressure.

Fig. 2.

Sympathetic responses to steady-state systemic nitroprusside (NTP). Data are means ± SE from n = 13. Data were analyzed with a 2-way repeated-measures ANOVA to determine the main effect of relative cluster size (10–100% of total clusters) and condition (baseline, drug) and the interaction of cluster and condition. A: probability of a relative cluster (10–100% of total clusters) firing once per integrated MSNA burst. B: probability of a relative cluster (10–100% of total clusters) firing more than once per integrated MSNA burst. *P < 0.05 vs. baseline.

Fig. 3.

Representative sample of data from 1 subject (26 yr, 21 kg/m²) collected at baseline and during phenylephrine infusion at the highest dose (0.6 µg·kg⁻¹·min⁻¹).

Fig. 4.

Sympathetic responses to steady-state systemic phenylephrine (PE). Data are means ± SE from n = 9. Data were analyzed with a 2-way repeated-measures ANOVA to determine the main effect of relative cluster size (10–100% of total clusters) and condition (baseline, drug) and the interaction of cluster and condition. A: probability of a relative cluster (10–100% of total clusters) firing once per integrated MSNA burst. B: probability of a relative cluster (10–100% of total clusters) firing more than once per integrated MSNA burst.

Fig. 5.

Representative sample of data from 1 subject (24 yr, 24 kg/m²) collected at baseline and during the modified Oxford procedure.

Fig. 6.

Sympathetic responses to the modified Oxford procedure. Data are means ± SE from n = 9. Data were analyzed with a 2-way repeated-measures ANOVA to determine the main effect of relative cluster size (10–100% of total clusters) and condition (baseline, drug) and the interaction of cluster and condition. A: probability of a relative cluster (10–100% of total clusters) firing once per integrated MSNA burst. B: probability of a relative cluster (10–100% of total clusters) firing more than once per integrated MSNA burst.

Fig. 7.

Synaptic delays during systemic infusions. A: steady-state nitroprusside (NTE; n = 13). B: steady-state phenylephrine (PE; n = 9). C: modified Oxford (n = 9). Sample sizes for clusters in which not all subjects are included (clusters were not present) are indicated. Data are means ± SE. Data were analyzed with a 2-way repeated-measures ANOVA to determine the main effect of relative cluster size (10–100% of total clusters) and condition (baseline, drug) and the interaction of cluster and condition.