Postexercise hypotension: central mechanisms

Abstract

A single bout of exercise can lead to a postexercise decrease in blood pressure in hypertensive individuals, called postexercise hypotension. Compelling evidence suggests that the central baroreflex pathway plays a crucial role in the development of postexercise hypotension. This review focuses on the exercise-induced changes in brainstem nuclei involved in blood pressure regulation.

Figure 1

A simplified schematic illustrating the brainstem baroreflex pathway. The baroreceptor afferent fibers, carrying blood pressure information, make excitatory synaptic contact with second-order neurons in the nucleus tractus solitarii (NTS), the first central site that receives and integrates the sensory inputs. The afferent fibers from skeletal muscle also project to the NTS through a poly-synapse pathway. These ascending fibers carrying information from the muscles make excitatory synaptic contact with the GABAergic interneurons in the NTS. The NTS output neurons convey signals from the baroreceptors and muscle afferents to neurons in the caudal ventral lateral medulla (CVLM) via excitatory glutamatergic synapses. The neuronal output of the CVLM provides the major inhibitory (GABAergic) inputs to the cardiovascular sympathetic neurons in the rostral ventral lateral medulla (RVLM), the major output neurons that regulate sympathetic nerve activity.

Figure 2

A single bout of dynamic exercise decreases the frequency of spontaneous inhibitory postsynaptic currents (sIPSC) recorded from second-order baroreceptive nucleus tractus solitarii (NTS) neurons in spontaneously hypertensive rats. Incubation with neuronkinin-1 receptor (NK1-R) antagonist significantly reduces the sIPSC frequency in the sham but not the postexercise hypotension (PEH) group. Numbers in parentheses indicate number of neurons. * p<0.05, Fisher's LSD test. [Adapted from Chen C-Y, Bechtold AG, Tabor J, Bonham AC. Exercise reduces GABA synaptic input onto nucleus tractus solitarii baroreceptor second-order neurons via NK1 receptor internalization in spontaneously hypertensive rats. J. Neurosci. 2009; 29(9):2754-2761. Copyright © 2009 Society for Neuroscience. Used with permission.]

Figure 3

A. Example images from one sham (A1) and one postexercise hypotension (PEH) (A2) rat. a, neuronkinin-1 receptor (NK1-R) staining (red color). b, glutamic acid decarboxylase (GAD 67) staining (green color). c, SYTOX staining (blue color). d, Overlap of a, b, and c. B. Fluorescent intensity plot across the white lines in A1d and A2d. PEH is associated with a higher degree of NK1-R internalization on nucleus tractus solitarii (NTS) γ-aminobutyric acid (GABA) neurons. [Adapted from Chen C-Y, Bechtold AG, Tabor J, Bonham AC. Exercise reduces GABA synaptic input onto nucleus tractus solitarii baroreceptor second-order neurons via NK1 receptor internalization in spontaneously hypertensive rats. J. Neurosci. 2009; 29(9):2754-2761. Copyright © 2009 Society for Neuroscience. Used with permission.]

Figure 4

Group data showing bicuculline-induced maximal increases in rostral ventral lateral medulla (RVLM) neuronal activity in postexercise hypotension (PEH) and sham groups. The maximal bicuculline-induced increase in RVLM neuronal firing activity (closed bars) over the baseline firing activity (open bars) is significantly greater in neurons in the PEH group compared to the sham group. Resting unit activity is significantly lower in PEH compared to sham. Maximal unit activity is not significantly different between the two groups. [Adapted from Kajekar R. Chen C-Y, Mutoh T, Bonham AC. GABA_A receptor activation at medullary sympathetic neurons contributes to postexercise hypotension. Am J Physiol Heart Circ Physiol. 2002; 282:H1615–H1624. Copyright © 2002 the American Physiological Society. Used with permission.]

Figure 5

A simplified schematic illustrating the interaction between substance P and γ-aminobutyric acid (GABA) transmissions in the nucleus tractus solitarii (NTS) on blood pressure regulation before, during and after exercise. During exercise, muscle afferent releases substance P to activate the NTS GABA interneurons to reset baroreflex to a higher level (exercise pressor response). Activation of the neurokinin-1 receptor (NK1-R) during exercise triggers the receptor to undergo internalization, which dampens the NTS GABA interneurons and resets baroreflex to a lower level after exercise (postexercise hypotension). [Adapted from Chen C-Y, Bechtold AG, Tabor J, Bonham AC. Exercise reduces GABA synaptic input onto nucleus tractus solitarii baroreceptor second-order neurons via NK1 receptor internalization in spontaneously hypertensive rats. J. Neurosci. 2009; 29(9):2754–2761. Copyright © 2009 Society for Neuroscience. Used with permission.]