Activity of muscle sympathetic neurons during normotensive pregnancy

Abstract

In pathological populations, elevated sympathetic activity is associated with increased activity of individual sympathetic neurons. We used custom action potential detection software to analyze multiunit sympathetic activity in 18 normotensive pregnant women (third trimester; 33 ± 5 wk) and 19 nonpregnant women at rest and a subset (10 and 13, respectively) during a cold pressor challenge. Although the number of action potentials per burst and number of active amplitude-based "clusters" were not different between groups, the total number of sympathetic action potentials per minute was higher in pregnant women at rest. Individual clusters were active predominately once per burst, suggesting they represent single neurons. Action potentials occurred in closer succession in normotensive pregnant (interspike interval 36 ± 10 ms) versus nonpregnant women (50 ± 27 ms; P < 0.001) at rest. Pregnant women had a lower total peripheral resistance (11.7 ± 3.0 mmHg·l^-1·min) than nonpregnant women (15.1 ± 2.7 mmHg·l^-1·min; P < 0.001), indicating a blunted neurovascular transduction. The cold pressor reduced the number of action potentials per burst in both groups due to shortening of the R-R interval in conjunction with increased burst frequency; total neural firing per minute was unchanged. Thus elevated sympathetic activity during normotensive pregnancy is specific to increased incidence of multiunit bursts. This is likely due to decreased central gating of burst output as opposed to generalized increases in central drive. These data also reinforce the concept that pregnancy appears to be the only healthy state of chronic sympathetic hyperactivity of which we are aware.

Keywords: action potentials; microneurography; neural recruitments; pregnancy; sympathetic activity.

Fig. 1.

Schematic of raw data from 1 nonpregnant woman. A: 30 s of continuous data, including ECG (lead II), blood pressure, integrated sympathetic nerve activity (SNA), raw SNA, and the de-noised neurogram, indicating identified sympathetic action potentials. The star identifies a burst of interest. B: the sympathetic action potentials identified within the burst of interest. Numbers refer to the cluster to which each action potential belongs. C: all action potential clusters identified across the entire analysis for this individual (i.e., 100 bursts). Clusters have been organized based on peak-to-peak amplitude, and action potentials belonging to each cluster have been overlaid to represent the mean waveform. In this individual, 9 unique action potential clusters were active within the identified burst of interest, with 3 of the clusters firing twice with the burst and 6 firing only once.

Fig. 2.

Schematic of raw data from 1 pregnant woman. A: 30 s of continuous data, including ECG (lead II), blood pressure, integrated sympathetic nerve activity (SNA), raw SNA, and the de-noised neurogram, indicating identified sympathetic action potentials. The star identifies a burst of interest. B: the sympathetic action potentials identified within the burst of interest. Numbers refer to the cluster to which each action potential belongs. C: all action potential clusters identified across the entire analysis for this individual (i.e., 100 bursts). Clusters have been organized based on peak-to-peak amplitude, and action potentials belonging to each cluster have been overlaid to represent the mean waveform. In this individual, 8 unique action potential clusters were active within the identified burst of interest, with 1 of the clusters firing twice with the burst and 7 firing only once.

Fig. 3.

A: histograms showing proportion of occurrences of a given action potential cluster associated with single or multiple firings in pregnant (white bars) and nonpregnant (black bars) women at rest. No differences in firing occurrence were found between groups. When a cluster was present within a burst of activity, the majority of these occurrences (~60%) was associated with only a single action potential. The occurrence of multiple firings from a given cluster was relatively low, with clusters contributing 2 action potentials ~23% of the time, 3 action potentials ~8% of the time, and 4+ action potentials ~9% of the time. B: during the cold pressor test (CPT), there was a reduction in the occurrence of multiple firings and an increase in a singular event. This was consistent between pregnant (n = 10) and nonpregnant women (n = 13). *Significant change in the percentage of occurrences during CPT, P < 0.01.

Fig. 4.

A: at rest, the number of action potentials per burst was not different between pregnant (C) and nonpregnant (@) women. However, even after controlling for the influence of the number of action potentials per burst, the interspike interval between action potentials was significantly lower in pregnant women (inset). B: during the cold pressor test, the interspike interval was reduced in nonpregnant women, and there were no longer any differences between groups. Scatter plots represent the mean values for each woman, including the regression between action potentials per burst and the interspike interval. Bar graph data are presented as means ± SD for each group.