Nucleus of the solitary tract catecholaminergic neurons modulate the cardiovascular response to psychological stress in rats

Abstract

Catecholaminergic neurons within the central nervous system are an integral part of stress-related neurocircuitry, and the nucleus of the solitary tract (NTS) plays a critical role in cardiovascular regulation. We tested the hypothesis that NTS catecholaminergic neurons attenuate psychological stress-induced increases in blood pressure and promote neuroendocrine activation in response to psychological stress.Anti-dopamine-β-hydroxylase antibody conjugated to the neurotoxin saporin (DSAP) or saline vehicle was microinjected into the NTS to lesion catecholaminergic neurons in male Sprague-Dawley rats, and 17 days later the rats were subjected to 60 min of restraint stress for five consecutive days. DSAP treatment significantly enhanced the integrated increase in mean arterial pressure during restraint on the first (800 ± 128 and 1115 ± 116 mmHg (min) for saline- and DSAP-treated rats) and fifth days (655 ± 116 and 1035 ± 113 mmHg (min) for saline- and DSAP-treated rats; P<0.01 for overall effect of DSAP treatment) of restraint. In contrast, after 60 min of restraint plasma corticosterone concentration was significantly lower in DSAP-treated compared with saline-treated rats (25.9 ± 7 compared with 46.8 ± 7 μg dl(-1) for DSAP- and saline-treated rats; P <0.05). DSAP treatment also significantly reduced baseline plasma adrenaline concentration (403 ± 69 compared with 73 ± 29 pg ml(-1) for saline- and DSAP-treated rats), but did not alter the magnitude of the adrenaline response to restraint. The data suggest that NTS catecholaminergic neurons normally inhibit the arterial pressure response, but help maintain the corticosterone response to restraint stress.

Figure 3. Baseline mean arterial pressure (A) and heart rate (B) measured 24 h per day and divided into the light and dark periods

Bilateral NTS microinjections of saline (filled squares and continuous lines) or DSAP (open triangles and dashed lines) were performed on day 8, and rats were subjected to daily restraint stress on days 21–25. Data for day 25 are not shown because the experiments ended after the morning stress on that day. †P≤ 0.05 compared with the baseline control period for saline-treated rats. *P≤ 0.05 compared with the pre-stress period for saline-treated rats. ‡P≤ 0.05 compared with the baseline control period for DSAP-treated rats.

Figure 1

Example photomicrographs from saline-treated (A, C, E and G) and DSAP-treated (B, D, F and H) rats for labelling of 11βHSD2-positive neurons in the NTS (A and B), or the DβH-positive neurons in the RVLM (C and D), locus coeruleus (E and F) or A5 region (G and H)

Figure 2. DβH-positive NTS (A and B) and ventrolateral medulla (C and D) neurons in a saline-treated rat (A and C) and a DSAP-treated rat (B and D)

The scale bars represent 200 μm.

Figure 4. Changes in mean arterial pressure (MAP; A) and heart rate (HR) in beats per minute (bpm; B) in response to 60 min of restraint stress and 30 min of recovery from stress on the first day (Day 21, left) and last day (Day 25, right) of repeated stress in saline-treated (continuous lines and squares) and DSAP-treated (dashed lines and open circles) rats

DSAP-mediated lesioning of NTS catecholaminergic neurons significantly enhanced the arterial pressure responses to stress and stress recovery (*P < 0.05). There were no effects of DSAP on the heart rate response to stress (B). The blood pressure and heart rate responses during the first 10 min of the recovery period were greater on day 25 compared with day 21 (†P < 0.05).

Figure 5. Spontaneous baroreceptor reflex (BRR) sensitivity determined by the sequence method (A), spectral analysis of blood pressure variability (BPV: B: very low frequency component, VLF; C: low frequency component, LF) and spectral analysis of heart rate variability (D: low frequency component, LF; E: high frequency component, HF; F: ratio of LF and HF)

†P < 0.05 for the fifth stress compared with the first stress; *P < 0.05 for the Saline compared with DSAP.

Figure 6. Linear regression analysis of the relationship between the number of catecholaminergic neurons in the NTS and the average integrated increase in mean arterial pressure during the first day of restraint stress in DSAP-treated rats

These factors were significantly correlated in the NTS as a whole (total, filled squares) as well as at the level of calamus scriptorius (CS, open triangles) and at 0.5 mm rostral to calamus scriptorius (CS + 0.5 mm, open circles), but not at 0.4 mm caudal to calamus scriptorius (CS – 0.4 mm, filled circles). The average values in the saline-treated rats are noted with an asterisk in each graph. Note the different scales on the x-axis.

Figure 7

Plasma concentrations for adrenaline (A), noradrenaline (B) and corticosterone (C) at baseline (time = 0) and at 10 and 60 min of novel restraint stress (*P < 0.05 for saline compared with DSAP)