Baroreflex

In cardiovascular physiology, the baroreflex or baroreceptor reflex is one of the body's homeostatic mechanisms for maintaining blood pressure. It provides a negative feedback loop in which an elevated blood pressure reflexively causes blood pressure to decrease; similarly, decreased blood pressure depresses the baroreflex, causing blood pressure to rise.

The system relies on specialized neurons (baroreceptors) in the aortic arch, carotid sinuses, and elsewhere to monitor changes in blood pressure and relay them to the brainstem. Subsequent changes in blood pressure are mediated by the autonomic nervous system.

Anatomy of the reflex
Baroreceptors include those in the auricles of the heart and vena cavae, but the most sensitive baroreceptors are in the carotid sinuses and aortic arch. The carotid sinus baroreceptors are innervated by the glossopharyngeal nerve (CN IX); the aortic arch baroreceptors are innervated by the vagus nerve (CN X). Baroreceptor activity travels along these nerves, which contact the nucleus of the solitary tract (NTS) in the brainstem.

The NTS sends excitatory fibers (glutamatergic) to the caudal ventrolateral medulla (CVLM), thus activating the CVLM. The activated CVLM then sends inhibitory fibers (GABAergic) to the rostral ventrolateral medulla (RVLM), thus inhibiting the RVLM. The RVLM is the primary regulator of sympathetic nervous system, sending excitatory fibers (catecholaminergic) to the sympathetic preganglionic neurons in the spinal cord. Hence, when the baroreceptors are activated (by an increased blood pressure), the NTS activates the CVLM, which in turn inhibits the RVLM, thus inhibiting the sympathetic branch of the autonomic nervous system leading to a decrease in blood pressure. Likewise, low blood pressure causes an increase in sympathetic tone via "disinhibition" (less inhibition, hence activation) of the RVLM.

The NTS also sends excitatory fibers to the Nucleus ambiguus (vagal nuclei) that regulate the parasympathetic nervous system, aiding in the decrease in sympathetic activity during conditions of elevated blood pressure.

Baroreceptor activation
The baroreceptors are stretch-sensitive mechanoreceptors. When blood pressure rises, the carotid and aortic sinuses are distended, resulting in stretch and therefore activation of the baroreceptors. Active baroreceptors fire action potentials ("spikes") more frequently than inactive baroreceptors. The greater the stretch, the more rapidly baroreceptors fire action potentials.

These action potentials are relayed to the nucleus of the tractus solitarius (NTS), which uses frequency as a measure of blood pressure. As discussed previously, increased activation of the NTS inhibits the vasomotor center and stimulates the vagal nuclei. The end result of baroreceptor activation is inhibition of the sympathetic nervous system and activation of the parasympathetic nervous system.

The sympathetic and parasympathetic branches of the autonomic nervous system have opposing effects on blood pressure. Sympathetic activation leads to an elevation of total peripheral resistance and cardiac output via increased contractility of the heart, heart rate, and arterial vasoconstriction, which tends to increase blood pressure. Conversely, parasympathetic activation leads to a decreased cardiac output via decrease in contractility and heart rate, resulting in a tendency to decrease blood pressure.

By coupling sympathetic inhibition and parasympathetic activation, the baroreflex maximizes blood pressure reduction. Sympathetic inhibition leads to a drop in peripheral resistance, while parasympathetic activation leads to a depressed heart rate and contractility. The combined effects will dramatically decrease blood pressure.

Similarly, sympathetic activation with parasympathetic inhibition allows the baroreflex to elevate blood pressure.

CVRx, Inc., a private company located in Minneapolis, Minnesota, has developed an implantable device to treat patients with high blood pressure that cannot be controlled with medications (resistant hypertension) by electrically activating the baroreceptors. This investigational device is called the Rheos Baroreflex Hypertension Therapy System. It is currently under evaluation in an FDA-regulated, phase III clinical trial.

Set point and tonic activation
Baroreceptors are active above the baroreceptor set point at mean arterial pressures (MAP) above approximately 70 mm Hg. When MAP falls below the set point, baroreceptors are almost silent. The baroreceptor set point is not fixed; its value may change with changes in blood pressure. For example, in hypertension, the set point will increase; on the other hand, hypotension will result in a depression of the baroreceptor set point.

At a MAP below approximately 50 mm Hg, baroreceptors are completely silent.

Effect on heart rate variability
The baroreflex may be responsible for a part of the low-frequency component of heart rate variability, the so called Mayer waves, at 0.1 Hz [Sleight, 1995].