Mental stress: A novel cardiovascular risk factor

Table 3 Some recent laboratory studies on the cardiac effects of stress in animal studies

Ref.	Setting	Main results
Morais-Silva et al[207], 2019	Using a chronic SDS protocol followed by the social interaction test, authors identified Wistar rats as resilient or susceptible to SDS	Susceptible animals showed increased depressive-like behaviours with resting tachycardia and decreased HRV due to increased sympathetic tone in the heart and a less effective baroreflex. In contrast, resilient rats were protected from these alterations by increased vagal tone, resulting in greater HRV values
Batschauer et al[225], 2020	Male Wistar rats were divided into four groups: Control-SD, control-HFD, CVS-SD, and CVS-HFD. The control-HFD and CVS-HFD groups were fed with HFD for six weeks. The CVS-HFD and CVS-SD groups were exposed to a CVS protocol in the last ten days of the six weeks	HFD promoted metabolic disorders and increased angiotensin II and leptin blood levels (P < 0.05). CVS or HFD increased BP and the SNS modulation of the heart and vessels and decreased baroreflex activity (P < 0.05). Combining CVS and HFD exacerbated the cardiac SNS response and increased basal HR (P < 0.05)
Hinterdobler et al[261], 2021	Cell-tracking experiments in animal models of acute mental stress	In mice in which leucocytes deplete rapidly from the blood after a single episode of acute mental stress, stress exposure leads to prompt uptake of inflammatory leucocytes from the blood to distinct tissues including heart, and, if present, atherosclerotic plaques. Acute stress enhances leucocyte influx into mouse atherosclerotic plaques by modulating endothelial cells and increases adhesion molecule expression and chemokine release through locally derived norepinephrine. Either chemical or surgical disruption of norepinephrine signalling diminished stress-induced leucocyte migration into mouse atherosclerotic plaques
Wu et al[233], 2021	PTSD and the potential association with the activities of the RVLM and the Mhb were studied. Multi-channel in vivo recordings were used to simultaneously acquire spontaneous neuronal firing and peripheral physiological indices, and FG retrograde tracing technique was used to observe the projections of labelled neurons in the Mhb	The discharge frequency of RVLM and Mhb neurons, the SBP, and the MAP in the PTSD group were all increased significantly compared with those in control group (P < 0.05). Mhb neurons were retrogradely labelled by FG through microinjection into the RVLM. In the control group, electrical stimulation in the Mhb increased HR at 100-300 μA (P < 0.05), elevated SBP and MAP at 200-300 μA (P < 0.05) and remarkably increased the RVLM neuronal discharge frequency at 100-500 μA (P < 0.05 or P < 0.01). In the PTSD group, however, only the discharge frequency of RVLM neurons was increased by the electrical stimulation at 100-300 μA (P < 0.05)
Bangsumruaj et al[219], 2022	Adult male Sprague Dawley rats exposed to 4-week CMS were used as an animal model for daily stress exposure in humans	CMS had lower body weight and higher sucrose intake. The HRV revealed that CMS increased autonomic activity without affecting its balance. The increased RAAS activity with upregulated angiotensin type 1 receptor mRNA expression was shown in CMS and correlated with stress
Duarte et al[100], 2023	Adult rats subjected to a 10-day protocol of RRS, habituating] or CVS (non-habituating) during adolescence, adulthood, or repeated exposure to either RRS or CVS in adolescence and adulthood	CVS increased basal circulating corticosterone levels and caused adrenal hypertrophy in the adolescence + adulthood group, an effect not identified in animals subjected to this stressor only in adulthood or adolescence. CVS also caused a sympathetically mediated resting tachycardia in the adulthood group. Moreover, the impairment in baroreflex function observed in the adulthood group subjected to CVS was shifted to an improvement in animals subjected to repeated exposure to this stressor during adolescence and adulthood
Wu et al[214], 2023	A compound stress method combining electrical stimulation and single prolonged stress was used to prepare a PTSD model, and the difference of weight gain before and after modelling and the elevated plus maze were used to assess the PTSD model. In addition, the distribution of retrogradely labelled neurons was observed using the FG retrograde tracking technique. To further investigate the effects, ACSF, non-selective amygdala glutamate receptors blocker KYN and AMPA receptor blocker CNQX were microinjected into the CeA in the PTSD rats	Compared with the control group, the PTSD group exhibited significantly lower weight gain (P < 0.01) and significantly decreased ratio of open arm time (P < 0.05). Retrograde labelling of neurons was observed in the CeA after microinjection of 0.5 μL FG in the RVLM. The content of AMPA receptor in the PTSD group was lower than that in the control group (P < 0.05), while there was no significant difference in RVLM neuron firing frequency and HR following ACSF injection. However, increases in RVLM neuron firing frequency and HR were observed after the injection of KYN or CNQX into the CeA (P < 0.05) in the PTSD group
Scott et al[215], 2025	Authors employed CSDS in adult male mice. CSDS results in increases in body mass, that are accompanied by elevated lean and fluid mass, as well as several somatic indices of chronic stress. Moreover, mice exposed to CSDS exhibit increased anxiety-like behaviour, spending more time in the closed arms of the elevated plus maze and less time in the center of an open field arena	Initial social defeat sessions result in increases in BP, activity, and temperature in comparison with control mice. Interestingly, while BP returns to basal levels by the start of the light cycle for the first few days of defeat, 14 days of CSDS results in sustained BP elevations, lower activity and lower body temperature. Finally, the results of HRV, spontaneous baroreflex sensitivity and adrenal transcriptome analyses were consistent with CSDS-induced autonomic dysfunction

SDS: Social defeat stress; HRV: Heart rate variability; RRS: Repeated restraint stress; CVS: Chronic variable stress; HR: Heart rate; LF: Low frequency; SBP: Systolic blood pressure; SD: Standard chow diet; HFD: High fat diet; BP: Blood pressure; SNS: Sympathetic nervous system; PTSD: Post-traumatic stress disorder; RVLM: Rostral ventrolateral medulla; Mhb: Medial habenular nucleus; FG: FluoroGold; MAP: Mean arterial pressure; CMS: Chronic mild stress; RAAS: Renin angiotensin aldosterone system; ACSF: Artificial cerebrospinal fluid; KYN: Kynurenic acid; CeA: Central nucleus of the amygdala; CSDS: Chronic social defeat stress.