Pharmacological Assessment of the Contribution of the Arterial Baroreflex to Sympathetic Discharge Patterns in Healthy Humans
Authors: Ott Elizabeth P. , Baker Sarah E. , Nicholson Wayne T. , Joyner Michael J. , Shoemaker Kevin , Limberg Jacqueline K. 
Published: June 2021

Objective

We examined the contribution of the arterial baroreflex to sympathetic discharge patterns in humans by systematically manipulating the reflex using intravenous nitroprusside and phenylephrine. We hypothesized nitroprusside would increase firing of low‐threshold axons, with no effect on recruitment of latent axons and/or synaptic delays. We further hypothesized phenylephrine would decrease firing of low‐threshold axons, with no effect on synaptic delays.

Methods

Heart rate (HR, ECG), arterial blood pressure (BP, brachial arterial catheter), and multi‐unit muscle sympathetic nerve activity (MSNA, microneurography of the peroneal nerve) were measured in 13 male subjects (30±2 yrs, 25±1 kg/m2) at baseline and during systemic intravenous infusion of nitroprusside (0.4–1.7 μg/kg/min) and phenylephrine (0.2–1.0 μg/kg/min), administered separately. Action potential (AP) patterns were studied from the filtered raw signal using wavelet‐based methodology.

Results

Compared to baseline, BP decreased and HR and multi‐unit MSNA (41±5 to 53±4 bursts/100 heart beats) increased with nitroprusside (all P<0.01). Nitroprusside increased AP incidence (326±66 to 579±129 AP/100 heart beats) and AP content per integrated burst (8±1 to 11±2 AP/burst) (all P<0.01). The firing probability of low‐threshold axons increased with nitroprusside, and recruitment of previously latent, high‐threshold axons was observed (22±3 to 24±3 max clusters, 9±1 to 11±1 clusters/burst; all P<0.05). Compared to baseline, BP increased and HR and multi‐unit MSNA (41±3 to 21±3 bursts/100 heart beats) decreased with phenylephrine (all P<0.01). Phenylephrine decreased AP discharge rate (406±128 to 166±42 AP/100 heart beats) and resulted in fewer unique clusters (15±2 to 9±1 max clusters, all P<0.05); however, components of an integrated burst were not altered (9±2 vs 8±1 AP/burst; 5±1 vs 4±1 clusters/burst, P>0.05). AP cluster latency decreased with cluster size under both conditions (P<0.01), but this relationship was not altered with nitroprusside (P=0.42) or phenylephrine (P=0.39).

Conclusions

Baroreflex unloading with systemic nitroprusside increases sympathetic neuronal discharge rate by increasing the firing probability of low‐threshold axons, in addition to recruitment of previously latent, high‐threshold axons. In contrast, baroreflex loading with systemic phenylephrine decreases neuronal discharge rate, including decreased firing probability of high‐threshold axons; however, the components of an integrated burst (AP and clusters per burst) and synaptic delays are unaffected. These data support a hierarchical pattern of sympathetic neural recruitment/de‐recruitment and suggest acute modification of synaptic delays are not influenced by the baroreflex.

Support or Funding Information

NIH HL083947, NIH HL130339

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.