Central 5‐HT<sub>7</sub>receptors are critical for reflex activation of cardiac vagal drive in anaesthetized rats

Kellett, Daniel O.; Ramage, Andrew G.; Jordan, David L.

doi:10.1113/jphysiol.2004.076521

Cited by 43 publications

(41 citation statements)

References 46 publications

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“…This apparent discrepancy could be explained by lack of vagal tone on the heart in anesthetized animals (24). Moreover, other excitatory neurotransmitters (e.g., serotonin) have been implicated in the nAmb in mediating reflexly induced bradycardia (19); in this case, microinjections of iGLUR antagonists in the nAmb are not expected to increase baseline HR, consistent with our observations. Blockade of spinal iGLURs decreased baseline HR and AP.…”

Section: Discussionsupporting

confidence: 80%

Cold pressor test in the rat: medullary and spinal pathways and neurotransmitters

Nakamura

Kawabe

Sapru³

2008

American Journal of Physiology-Heart and Circulatory Physiology

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This study was designed to delineate the medullary and spinal pathways mediating the cardiovascular responses to cold pressor test (CPT) and to identify neurotransmitters in these pathways. Experiments were done in barodenervated, urethane-anesthetized, male Wistar rats. The CPT was performed by immersing the limbs and ventral half of the body of the rat in ice-cold water (0.5 degrees C) for 2 min. CPT elicited an immediate increase in mean arterial pressure (MAP), heart rate (HR), and greater splanchnic nerve activity (GSNA). Bilateral blockade of ionotropic glutamate receptors (iGLURs) in the rostral ventrolateral medullary pressor area (RVLM) significantly attenuated the CPT-induced responses. Bilateral blockade of gamma-aminobutyric acid (GABA) receptors, but not iGLURs, in the nucleus ambiguus (nAmb) significantly reduced the CPT-induced increases in HR, but not MAP. Blockade of spinal iGLURs caused a significant reduction in CPT-induced increases in MAP and GSNA, whereas the increases in HR were reduced to a lesser extent. Combination of the blockade of spinal iGLURs and bilateral vagotomy or intravenous atropine almost completely blocked CPT-induced tachycardia. Midcollicular decerebration significantly reduced CPT-induced increases in MAP and HR. These results indicated that: 1) CPT-induced increases in MAP, HR, and GSNA were mediated by activation of iGLURs in the RVLM and spinal cord, 2) activation of GABA receptors in the nAmb also contributed to the CPT-induced tachycardic responses, and 3) brain areas rostral to the brain stem also participated in the CPT-induced pressor and tachycardic responses.

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Section: Discussionsupporting

confidence: 80%

Cold pressor test in the rat: medullary and spinal pathways and neurotransmitters

Nakamura

Kawabe

Sapru³

2008

American Journal of Physiology-Heart and Circulatory Physiology

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“…Different 5HT receptors have been shown to play diverse roles in cardiorespiratory function in the brainstem (Ramage, 2001). Central 5HT7 receptors are involved in the reflex activation of parasympathetic outflow to the heart upon stimulating cardiopulmonary afferent fibers, arterial baroreceptors and chemoreceptor afferents (Kellett et al, 2005). Central 5HT1A receptors are also involved in mediating both cardiopulmonary and baroreceptor reflex evoked vagal bradycardia, but may not be involved in chemoreceptor elicited responses in cardiac vagal neurons (Skinner et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

5HT2 receptor activation facilitates P2X receptor mediated excitatory neurotransmission to cardiac vagal neurons in the nucleus ambiguus

et al. 2008

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SummaryParasympathetic preganglionic cardiac vagal neurons (CVNs) which dominate the control of heart rate are located within the nucleus ambiguus (NA). Serotonin (5HT), and in particular 5HT2 receptors, play an important role in cardiovascular function in the brainstem. However, there is a lack of information on the mechanisms of action of 5HT2 receptors in modulating parasympathetic cardiac activity. This study tests whether activation of 5HT2 receptors alters excitatory glutamatergic and purinergic neurotransmission to CVNs. Application of α-methyl-5-hydroxytryptamine (α-Me-5HT), a 5HT2 agonist, reversibly increased both the frequency and amplitude of miniature excitatory postsynaptic currents (mEPSCs) in CVNs. Similar responses were obtained with alphamethyl-5-(2-thienylmethoxy)-1H-indole-3-ethanamine hydrochloride (BW723C86), and mchlorophenylpiperazine (m-CPP), 5HT2B and 5HT2B/C receptor agonists, respectively. The facilitation evoked by α-Me-5HT was prevented by the 5HT2B/C receptor antagonist SB206553 hydrochloride (SB206553). Interestingly, the blockage of both NMDA and non-NMDA glutamatergic receptors did not prevent α-Me-5HT-evoked facilitation of mEPSCs, however, the responses were blocked by the P2 receptor antagonist pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid (PPADS). The responses evoked by α-Me-5HT were mimicked by application of α,β-methylene ATP (α,β-Me-ATP), a P2X receptor agonist, which were also blocked by PPADS. In summary, these results indicate activation of 5HT2 receptors facilitates excitatory purinergic, but not glutamatergic, neurotransmission to CVNs.

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“…Central 5-HT 7 receptors play an important role in the reflex activation of parasympathetic outflow to the heart upon stimulating cardiopulmonary afferent fibers, arterial baroreceptors and chemoreceptor afferents (Kellett et al, 2005). Central 5-HT 1A receptors are also involved in mediating both cardiopulmonary and baroreceptor reflex evoked vagal bradycardia, but may not be involved in chemoreceptor elicited responses in cardiac vagal neurons (Skinner et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

5-HT2 receptor subtypes mediate different long-term changes in GABAergic activity to parasympathetic cardiac vagal neurons in the nucleus ambiguus

et al. 2007

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Serotonin (5-HT), and in particular 5-HT 2 receptors, play an important role in cardiorespiratory function within the brainstem. In addition, abnormalities in the 5-HT system have been implicated in many cardiorespiratory disorders, including sudden infant death syndrome. However little is known about the mechanisms of action of 5-HT 2 receptors in altering the activity of parasympathetic cardiac neurons in the brainstem. In this study we examined the effects of activation of different subtypes of 5-HT 2 receptors on spontaneous and respiratory evoked GABAergic neurotransmission to cardioinhibitory vagal neurons within the nucleus ambiguus as well as rhythmic fictive inspiratoryrelated activity. A single application of α-Me-5-hydroxytryptamine maleate (α-Me-5-HT), a 5-HT 2 receptor agonist, did not significantly alter the frequency of spontaneous or respiratory-evoked GABAergic inhibitory post-synaptic currents (IPSCs) in cardiac vagal neurons. However, repetitive successive applications of α-Me-5-HT elicited a long-lasting (≥ 1 hour) decrease in the frequency of spontaneous as well as inspiratory-related GABAergic IPSCs to cardiac vagal neurons. This study demonstrates multiple, but not single applications of the 5-HT 2 receptor agonist α-Me-5-HT caused a long-lasting inhibition of both spontaneous and fictive inspiratory-related GABAergic neurotransmission to CVNs which can be prevented by the 5-HT 2B receptor antagonist SB204741, but persisted with the 5-HT 2A/2C receptor antagonist ketanserin. The 5-HT 2 receptor agonist α-Me-5-HT also reversibly and transiently excited central fictive inspiratory activity which was abolished by ketanserin, but was unaffected by the 5-HT 2B receptor antagonist SB204741.

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Central 5‐HT₇receptors are critical for reflex activation of cardiac vagal drive in anaesthetized rats

Cited by 43 publications

References 46 publications

Cold pressor test in the rat: medullary and spinal pathways and neurotransmitters

Cold pressor test in the rat: medullary and spinal pathways and neurotransmitters

5HT2 receptor activation facilitates P2X receptor mediated excitatory neurotransmission to cardiac vagal neurons in the nucleus ambiguus

5-HT2 receptor subtypes mediate different long-term changes in GABAergic activity to parasympathetic cardiac vagal neurons in the nucleus ambiguus

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Central 5‐HT7receptors are critical for reflex activation of cardiac vagal drive in anaesthetized rats

Cited by 43 publications

References 46 publications

Cold pressor test in the rat: medullary and spinal pathways and neurotransmitters

Cold pressor test in the rat: medullary and spinal pathways and neurotransmitters

5HT2 receptor activation facilitates P2X receptor mediated excitatory neurotransmission to cardiac vagal neurons in the nucleus ambiguus

5-HT2 receptor subtypes mediate different long-term changes in GABAergic activity to parasympathetic cardiac vagal neurons in the nucleus ambiguus

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Central 5‐HT₇receptors are critical for reflex activation of cardiac vagal drive in anaesthetized rats