What are the neural and hormonal mechanisms regulating heart rate?

From the Guidelines

The heart rate is regulated through a complex interplay of neural and hormonal mechanisms, with the autonomic nervous system providing primary neural control, and the endocrine system playing a crucial role in hormonal regulation, as evident from the most recent study in 2024 1. The autonomic nervous system, comprising the sympathetic and parasympathetic branches, acts in conjunction with the central nervous system to regulate heart dynamics through different reflex pathways that combine efferent and afferent information.

• The sympathetic system releases norepinephrine to increase heart rate, while the parasympathetic system, via the vagus nerve, releases acetylcholine to slow the heart rate.
• These neural signals directly affect the sinoatrial (SA) node, the heart's natural pacemaker.
• The intrinsic cardiac nervous system, comprising afferent, efferent, and local circuit neurons, plays a crucial role in regulating heart function, with afferent neurons relaying information about mechanical and chemical changes in the heart, and efferent neurons providing control over heart muscle fibers and coronary vessels.
• Hormonal regulation occurs primarily through the endocrine system, with epinephrine and norepinephrine from the adrenal medulla increasing heart rate during stress or exercise, and other hormones like thyroid hormones and atrial natriuretic peptide also influencing heart rate.
• The baroreceptor reflex and chemoreceptors are essential regulatory mechanisms that detect changes in blood pressure and blood oxygen, carbon dioxide, and pH levels, triggering neural responses to adjust heart rate and maintain proper tissue oxygenation.
• The most recent study in 2024 1 highlights the importance of the neurovisceral integration model, which proposes that the autonomic nervous system interacts dynamically with the central nervous system to promote control of the heart, and that high-level cognitive processes can influence heart rate.

From the FDA Drug Label

Atropine-induced parasympathetic inhibition may be preceded by a transient phase of stimulation, especially on the heart where small doses first slow the rate before characteristic tachycardia develops due to paralysis of vagal control Atropine exerts a more potent and prolonged effect on heart, intestine and bronchial muscle than scopolamine, but its action on the iris, ciliary body and certain secretory glands is weaker than that of scopolamine. The receptors antagonized by atropine are the peripheral structures that are stimulated or inhibited by muscarine (i.e., exocrine glands and smooth and cardiac muscle). Metoprolol is a beta 1-selective (cardioselective) adrenergic receptor blocker. Animal and human experiments indicate that metoprolol slows the sinus rate and decreases AV nodal conduction

The neural and hormonal mechanisms regulating heart rate involve the parasympathetic and sympathetic nervous systems. The parasympathetic nervous system uses acetylcholine as a neurotransmitter to slow the heart rate, while the sympathetic nervous system uses catecholamines (such as epinephrine) to increase the heart rate.

• Atropine antagonizes the effects of acetylcholine on the heart, leading to an increase in heart rate due to paralysis of vagal control 2.
• Metoprolol blocks the effects of catecholamines on the heart, leading to a decrease in heart rate by slowing the sinus rate and decreasing AV nodal conduction 3.

From the Research

Neural Mechanisms

• The autonomic nervous system (ANS) plays a key role in regulating heart rate variability (HRV) through the interplay of sympathetic and parasympathetic systems 4
• The cardio-accelerating center, lungs, and non-striated muscles are innervated by cardiac sympathetic nerves, which stimulate the heart via the cervicothoracic ganglion and vagus nerve 4
• The analysis of HRV is a non-invasive technique to identify the functioning of the ANS, providing reliable information about the interaction of the sympathetic and parasympathetic nervous systems 4

Hormonal Mechanisms

• Beta-blockers antagonize β-adrenergic receptors, which receive stimulus from endogenous catecholamines, ultimately leading to cardiac contraction or vascular dilation 5
• The sympathetic nervous system (SNS) provides inotropic support to the failing heart, increasing stroke volume, and peripheral vasoconstriction to maintain mean arterial perfusion pressure 6
• Activation of SNS has been attributed to withdrawal of normal restraining influences and enhancement of excitatory inputs, including changes in peripheral baroreceptor and chemoreceptor reflexes, chemical mediators, and central integratory sites 6

Regulation of Heart Rate

• HRV is influenced by various variables, including pathological, physiological, psychological, environmental factors, lifestyle factors, and genetic factors 4
• The dynamic control mechanism of heart rate is a stable fixed point, rather than a strange attractor or transitions between a fixed point and a limit cycle, and HR slope (amplitude) may depend on the ratio of cardiac disturbance or metabolic demand mean to myocardial electrical resistance (PNS-SNS activity) 7
• Aconitine and related alkaloids can affect heart rate by acting on voltage-sensitive sodium channels, causing a persistent activation of the sodium channels, which become refractory to excitation, leading to arrhythmias 8