Neurogenic Background for Emotional Stress-Associated Hypertension

Abstract

Purpose of review: The response to natural stressors involves both cardiac stimulation and vascular changes, primarily triggered by increases in sympathetic activity. These effects lead to immediate flow redistribution that provides metabolic support to priority target organs combined with other key physiological responses and cognitive strategies, against stressor challenges. This extremely well-orchestrated response that was developed over millions of years of evolution is presently being challenged, over a short period of time. In this short review, we discuss the neurogenic background for the origin of emotional stress-induced hypertension, focusing on sympathetic pathways from related findings in humans and animals.

Recent findings: The urban environment offers a variety of psychological stressors. Real or anticipatory, emotional stressors may increase baseline sympathetic activity. From routine day-to-day traffic stress to job-related anxiety, chronic or abnormal increases in sympathetic activity caused by emotional stressors can lead to cardiovascular events, including cardiac arrhythmias, increases in blood pressure and even sudden death. Among the various alterations proposed, chronic stress could modify neuroglial circuits or compromise antioxidant systems that may alter the responsiveness of neurons to stressful stimuli. These phenomena lead to increases in sympathetic activity, hypertension and consequent cardiovascular diseases. The link between anxiety, emotional stress, and hypertension may result from an altered neuronal firing rate in central pathways controlling sympathetic activity. The participation of neuroglial and oxidative mechanisms in altered neuronal function is primarily involved in enhanced sympathetic outflow. The significance of the insular cortex-dorsomedial hypothalamic pathway in the evolution of enhanced overall sympathetic outflow is discussed.

Keywords: Anxiety; Autonomic nervous system; Emotional stress; Hypertension; Sympathetic.

Fig. 1

Total world population, world urban population, world rural population and world population with hypertension; rates of change over approximately three decades (a). Approximate percentage of growth for each population in ~ 30 years interval (b). Note that the percentage of the population with hypertension in the past 3 decades grows accordingly to the growth of the urban population. Data extracted from World Urbanization Prospects: The 2018 Revision [2] and Worldwide trends in hypertension prevalence and progress in treatment and control from 1990 to 2019 [4]

Fig. 2

Mean maximum changes in heart rate (HR) (a) and mean arterial pressure (MAP) (b) caused by environment change stress in male Wistar rats (n = 6) treated with vehicle (white bars) or atenolol (black bars) during cage-switch stress (left drawing). In the experiment illustrated, the new cage was previously occupied by another male rat. Tachycardia is completely abolished in the group of rats that received previous treatment with beta-adrenergic antagonist, atenolol (intraperitoneal; 2 mg/kg). Note that the pressor response is completely preserved. See main text for discussion. (Ethics approval protocol number: 278/76/2017); t test, *P < 0.05

Fig. 3

Top-down control of sympathetic responses in the presence of an emotional stressor. In this hypothetical scheme, the presence of a stressor stimuli evokes a prompt sympathetic response evoking cardiac, vasomotor, and renal changes that are necessary for an optimal functional defensive reaction (a). In the abnormal circuit (b), note that the hypothetical stressor of same magnitude now evokes an enhanced sympathetic response given that the stimulus is boosted by hyperreactive circuits in emotion related regions (here represented by amygdala and/or cortical regions), enhancing excitatory activity in downstream pathways. “Plus” symbols ( +) indicate excitatory activity; Dashed arrows represent indirect projections. DMH, dorsomedial hypothalamus; PVN, paraventricular hypothalamus; RVLM, rostral ventrolateral medulla; Raphe: medullary raphe neurons; DP/DTT dorsal peduncular cortex and dorsal tenia tecta; DLPFC, dorsolateral prefrontal cortex. See main text for details

Fig. 4

SHR rats present marked alterations to the neurovascular unit within the IC (blue: astrocytes; green: microglia) and enhanced NMDA-mediated anatomical projections to the DMH (red: neurons retrogradely labeled from the DMH). These alterations may contribute to the maintenance of hypertension and altered behavior in SHR. See text for details. Scale bar: 30 µm. Experiments were conducted in accordance with NIH guidelines and carried out in agreement with Augusta University Institutional Animal Care and Use Committee Guidelines

Fig. 5

Schematic diagram for the effects of stress on ROS-mediated changes in neural pathways related to enhanced sympathetic outflow. Emotional stress increases ROS levels in neural pathways while reducing the activities of antioxidant enzymes resulting in enhanced activation of neurons in the amygdala, paraventricular nucleus, and rostral ventrolateral medulla (see Fig. 3), overall resulting in increased sympathetic outflow and concomitant hypertension