What are the effects of improved regulation of the sympathetic nervous system (SNS) and hypothalamic-pituitary-adrenal (HPA) axis?

From the Guidelines

To improve regulation of the sympathetic nervous system (SNS) and hypothalamic-pituitary-adrenal (HPA) axis, I recommend a comprehensive approach combining lifestyle modifications, stress management techniques, and potentially targeted supplements, prioritizing beta-blockers for patients with heart failure (HF) as they have been shown to reduce the risk of death in these patients, as evidenced by studies such as 1 and 1.

The effects of improved regulation of the SNS and HPA axis are multifaceted, including:

• Reduced chronic activation of stress response systems
• Promotion of parasympathetic activity
• Support for healthy neurotransmitter and hormone balance
• Decreased risk of cardiovascular problems, metabolic dysfunction, and mood disorders

Key lifestyle modifications include:

• Regular physical activity for 30 minutes daily, particularly moderate aerobic exercise, to modulate sympathetic activity and normalize cortisol patterns, as supported by 1 and 1
• Practice of daily mindfulness meditation or deep breathing exercises for 10-15 minutes to activate the parasympathetic nervous system
• Ensuring adequate sleep of 7-9 hours nightly with consistent sleep-wake times to support HPA axis function
• Maintaining a balanced diet rich in omega-3 fatty acids, antioxidants, and complex carbohydrates while limiting caffeine, alcohol, and processed foods

For patients with HF, beta-blockers such as bisoprolol, sustained-release metoprolol (succinate), and carvedilol have been shown to be effective in reducing the risk of death, as noted in 1 and 1. The choice of beta-blocker may depend on individual patient characteristics and the specific formulation used, with carvedilol potentially offering a survival benefit compared to metoprolol tartrate, as suggested by 1.

Overall, a comprehensive approach to regulating the SNS and HPA axis, incorporating lifestyle modifications, stress management techniques, and targeted supplements or medications as needed, can help mitigate the negative effects of chronic stress and promote overall health and well-being, as supported by the evidence from 1, 1, 1, and 1.

From the FDA Drug Label

The mechanism of the antihypertensive effects of beta-blocking agents has not been fully elucidated However, several possible mechanisms have been proposed: (1) competitive antagonism of catecholamines at peripheral (especially cardiac) adrenergic neuron sites, leading to decreased cardiac output; (2) a central effect leading to reduced sympathetic outflow to the periphery; and (3) suppression of renin activity

The effects of improved regulation of the sympathetic nervous system (SNS) and hypothalamic-pituitary-adrenal (HPA) axis are reduced sympathetic outflow to the periphery and suppression of renin activity, which may lead to decreased cardiac output and reduced blood pressure 2.

• Key effects:
  • Reduced sympathetic outflow to the periphery
  • Suppression of renin activity
  • Decreased cardiac output
  • Reduced blood pressure

From the Research

Effects of Improved Regulation of the SNS and HPA Axis

The effects of improved regulation of the sympathetic nervous system (SNS) and hypothalamic-pituitary-adrenal (HPA) axis include:

• Reduced evening cortisol, waking cortisol, ambulatory systolic blood pressure, resting heart rate, high frequency heart rate variability, fasting blood glucose, cholesterol, and low-density lipoprotein 3
• Improved regulation of the SNS and HPA system in various populations, which can lead to better management of stress and related physiological measures 3
• Containment of sympathoexcitation during stress, which may be an important mechanism of cardioprotection in certain populations 4
• Differential effects on systemic immune cells after severe experimental stroke, with the HPA axis having a more significant impact on lymphocytopenia and the SNS affecting interferon-γ secretion by lymphocytes 5

Mechanisms and Interactions

The mechanisms and interactions between the SNS and HPA axis include:

• Co-activation of SAM and HPA responses to acute stress, which can illuminate risk for development of internalizing and externalizing problems 6
• Interaction between SAM and HPA reactivity and recovery phases, which can predict internalizing and externalizing symptoms in adolescents 6
• Negative feedback of corticosteroids on the sympathetic axis, which may control the post-stroke stress reaction 5
• Differential sensitivity of immune cell populations to stress hormones, with glucocorticoid receptor (GCR) and beta2-adrenergic receptor (β2-AR) playing important roles 5

Population-Specific Effects

The effects of improved regulation of the SNS and HPA axis can vary across different populations, including:

• Pima Indians, who may have a lower SNS activity and be more responsive to the inhibitory effect of cortisol on MSNA 4
• Caucasians, who may have a higher SNS activity and be less responsive to the inhibitory effect of cortisol on MSNA 4
• Adolescents, who may experience differential effects of SAM and HPA co-activation on internalizing and externalizing problems 6