Role of Purinergic and Nicotinic Receptors in the Hypoxia/Hypercapnia Evoked Excitation of Parasympathetic Cardiac Vagal Neurons in the Brainstem
Article Outline
Abstract
Hypoxia and hypercapnia are among the strongest challenges to the cardiorespiratory system, and these responses are altered by prenatal nicotine exposure. However the mechanism(s) responsible for these cardiorespiratory responses, and their alteration by prenatal nicotine exposure are unknown. We used an in vitro medullary slice that allows simultaneous examination of rhythmic respiratory-related activity and synaptic neurotransmission to cardiac vagal neurons (CVNs) that control heart rate. Respiratory-related increases in excitatory neurotransmission only occurred upon recovery from hypoxia/hypercapnia in unexposed animals. These responses were mediated in part by purinergic receptors. Prenatal nicotine exposure transformed central cardiorespiratory responses; CVNs received a respiratory-related neurotransmission not during recovery but during hypoxia/hypercapnia which was wholly dependent upon nicotinic receptor activation. In the presence of nicotinic antagonists, the responses in prenatal nicotine animals reverted to the pattern of responses in unexposed animals. These data identify a new functional role for purinergic receptors in the cardiorespiratory responses to hypoxia/hypercapnia and their role in occluding nicotinic receptor activation with prenatal nicotine exposure. [Tzu Chi Med J 2008;20(1):1–10]
Keywords: Ambiguus , Cardiac , Nicotinic , Parasympathetic , Purinergic
No full text is available. To read the body of this article, please view the PDF online.
References
- . Respiratory variations of the heart rate II–the central mechanism of the respiratory sinus arrhythmia and the inter-relations between the central and the reflex mechanisms . Proc Royal Soc . 1936;119:218–232
- . Synaptic mechanisms involved in the inspiratory modulation of vagal cardio-inhibitory neurones in the cat . J Physiol . 1984;356:65–78
- . Prenatal nicotine exposure alters central cardiorespiratory responses to hypoxia in rats: implications for sudden infant death syndrome . J Neurosci . 2004;24:9261–9268
- . Respira tory sinus arrhythmia: endogenous activation of nicotinic receptors mediates respiratory modulation of brainstem cardioinhibitory parasympathetic neurons . Circ Res . 2003;93:565–572
- . Hypoxic apnea and gasping . J Clin Invest . 1975;56:1371–1377
- . Failure of autoresuscitation in weanling mice: significance of cardiac glycogen and heart rate regulation . J Appl Physiol . 1999;87:203–210
- . The cardiorespiratory response to anoxia: normal development and the effect of nicotine . Respir Physiol . 1997;109:231–239
- . Nervous control of heart rate: activity in the cardiac vagus of the dogfish . J Appl Physiol . 1982;53:1330–1335
- Anderson RN. Deaths: leading causes for 2000. National Vital Statistics Reports 2002:50.
- . Prenatal exposure to nicotine impairs protective responses of rat pups to hypoxia in an age-dependent manner . Respir Physiol . 2001;127:61–73
- . Cardiorespiratory recordings from infants dying suddenly and unexpectedly at home . Pediatrics . 1994;93:44–49
- Brainstem 3H-nicotine receptor binding in the sudden infant death syndrome . J Neuropathol Exp Neurol . 1998;57:1018–1025
- . Gasping and other cardiorespiratory patterns during sudden infant deaths . Pediatr Res . 1999;45:350–354
- . Frequency and timing of recurrent events in infants using home cardiorespiratory monitors . J Pediatr . 1998;132:783–789
- . Diminished respiratory sinus arrhythmia in asphyxiated term infants . Am J Obstet Gynecol . 1986;155:1263–1266
- . Finding the failure mechanism in sudden infant death syndrome . Nat Med . 1998;4:157–158
- Dynamic analysis of cardiac R-R intervals in normal infants and in infants who subsequently succumbed to the sudden infant death syndrome . Pediatr Res . 1992;31:606–612
- . Cardiorespiratory interactions in heart-rate control . Ann N Y Acad Sci . 1988;533:350–357
- Smoking and the sudden infant death syndrome . Pediatrics . 1993;91:893–896
- . Cigarette smoking as a risk factor for sudden infant death syndrome: a population-based study . Am J Public Health . 1990;80:29–32
- . Effects of autonomic blockade on the baroreflex in man at rest and during exercise . Circ Res . 1972;30:177–185
- . Reflex control of heart rate in the unanesthetized dog . Am J Physiol . 1970;218:780–789
- . Reflex discharge patterns of cardiac vagal efferent fibres . J Physiol . 1972;222:1–15
- . Arterial baroreflex control of heart rate in the conscious rat . Am J Physiol . 1980;238:H515–H520
- . Autonomic nervous system control of heart rate during baroreceptor activation in conscious and anesthetized rats . J Auton Nerv Syst . 1987;20:121–127
- . Neural organisation and control of the baroreceptor reflex . Rev Physiol Biochem Pharmacol . 1981;88:24–124
- . Autonomic control of cardiac pacemaker activity and atrioventricular transmission . J Appl Physiol . 1969;27:465–470
- . Identification and dissociation of cardiovascular neurons from the medulla for patch clamp analysis . Neurosci Lett . 1991;132:217–221
- . Firing properties of identified parasympathetic cardiac neurons in nucleus ambiguus . Am J Physiol . 1996;271:H2609–H2614
- . Voltage-gated currents in identified parasympathetic cardiac neurons in the nucleus ambiguus . Brain Res . 1996;739:258–262
- . Advances in parasympathetic control of heart rate and cardiac function . News Physiol Sci . 1999;14:155–161
- . Brainstem premotor cardiac vagal neurons . In: Nae Dun BM , Paul Pilowsky editor. Neural Mechanisms of Cardiovascular Regulation . Dordrecht, The Netherlands: Kluwer Academic Publishers; 2004;p. 371–397
- . Central nervous system regulation of the heart . In: Armour JLA Andrew editors. Basic and Clinical Neurocardiology . Oxford University Press; 2004;p. 187–219
- . Acetylcholine activates a nicotinic receptor and an inward current in dorsal motor nucleus of the vagus neurons in vitro . Neurosci Lett . 1995;195:163–166
- . Sensory afferent neuro-transmission in caudal nucleus tractus solitarius–common denominators . Chem Senses . 1996;21:387–395
- . Nicotine excites cardiac vagal neurons via three sites of action . Clin Exp Pharmacol Physiol . 1998;25:453–456
- . Stimulation of NTS activates NMDA and non-NMDA receptors in rat cardiac vagal neurons in the nucleus ambiguus . Brain Res . 1998;792:277–282
- . Nicotine enhances presynaptic and postsynaptic glutamatergic neurotransmission to activate cardiac parasympathetic neurons . Circ Res . 1998;83:1241–1247
- . Superior laryngeal neurons directly excite cardiac vagal neurons within the nucleus ambiguus . Brain Res Bull . 2000;51:135–138
- . Firing properties of identified superior laryngeal neurons in the nucleus ambiguus in the rat . Neurosci Lett . 2001;303:1–4
- . Characteristics of spontaneous and evoked GABAergic synaptic currents in cardiac vagal neurons in rats . Brain Res . 2001;889:78–83
- . Activity of cardiorespiratory networks revealed by transsynaptic virus expressing GFP . J Neurophysiol . 2001;85:435–438
- . Agatoxin-IVA-sensitive calcium channels mediate the presynaptic and postsynaptic nicotinic activation of cardiac vagal neurons . J Neurophysiol . 2001;85:164–168
- Synaptic and neurotransmitter activation of cardiac vagal neurons in the nucleus ambiguus . Ann N Y Acad Sci . 2001;940:237–246
- . Arginine vasopressin enhances GABAergic inhibition of cardiac parasympathetic neurons in the nucleus ambiguus . Neuroscience . 2002;111:699–705
- . Endomorphin-2 inhibits GABAergic inputs to cardiac parasympathetic neurons in the nucleus ambiguus . Neuroscience . 2002;113:975–983
- Ketamine inhibits presynaptic and postsynaptic nicotinic excitation of identified cardiac parasympathetic neurons in nucleus ambiguus . Anesthesiology . 2002;96:667–674
- . Ketamine inhibits sodium currents in identified cardiac parasympathetic neurons in nucleus ambiguus . Anesthesiology . 2002;96:659–666
- . Nociceptin inhibits gamma-aminobutyric acidergic inputs to cardiac parasympathetic neurons in the nucleus ambiguus . J Pharmacol Exp Ther . 2002;300:78–82
- Pentobarbital enhances GABAergic neurotransmission to cardiac parasympathetic neurons, which is prevented by expression of GABAA epsilon subunit . Anesthesiology . 2002;97:717–724
- . Distribution of mu-opioid receptors in rat visceral premotor neurons . Neuroscience . 2002;115:851–860
- Mu-opioid receptors are located postsynaptically and endomorphin-1 inhibits voltage-gated calcium currents in premotor cardiac parasympathetic neurons in the rat nucleus ambiguus . Neuroscience . 2003;116:573–582
- . Synaptic activation of cardiac vagal neurons by capsaicin sensitive and insensitive sensory neurons . Brain Res . 2003;979:210–215
- Endogenous acetylcholine and nicotine activation enhances GABAergic and glycinergic inputs to cardiac vagal neurons . J Neurophysiol . 2003;89:2473–2481
- . Glycinergic inputs to cardiac vagal neurons in the nucleus ambiguus are inhibited by nociceptin and muselective opioids . J Neurophysiol . 2003;90:1581–1588
- Fentanyl inhibits GABAergic neurotransmission to cardiac vagal neurons in the nucleus ambiguus . Brain Res . 2004;1007:109–115
- . Respiratory variations of the heart rate II–the central mechanism of the respiratory arrhythmia and the interrelationships between the central and reflex mechanisms . Proc Roy Soc . 1935;119:218–231
- . Some reflex cardioinhibitory responses in the cat and their modulation by central inspiratory neuronal activity . J Physiol . 1991;439:559–577
- . Effects of respiration on blood pressure and heart rate variability in humans . Clin Exp Pharmacol Physiol . 1991;18:735–742
- . Quantitative respiratory sinus arrhythmia analysis. A simple noninvasive, reimbursable measure of cardiac wellness and dysfunction . Ann N Y Acad Sci . 1991;618:67–101
- . Respiratory sinus arrhythmia in dogs. Effects of phasic afferents and chemostimulation . J Clin Invest . 1991;87:1621–1627
- . Power spectral analysis of heart rate variability in traumatic quadriplegic humans . Am J Physiol . 1990;258:H1722–H1726
- . Beat-bybeat modulation of AV conduction. II. Autonomic neural mechanisms . Am J Physiol . 1986;251:H1134–H1142
- . The baroreceptor input to cardiac vagal motoneurones . J Physiol . 1978;282:365–374
- . Breathing: rhythmicity, plasticity, chemosensitivity . Annu Rev Neurosci . 2003;26:239–266
- . Reconfiguration of the neural network controlling multiple breathing patterns: eupnea, sighs and gasps [see comment] . Nat Neurosci . 2000;3:600–607
- . Clinical correlates, natural history and outcome of neonatal apnoea . Semin Neonatol . 2004;9:205–211
- Absence of bradycardic response to apnea and hypoxia in heart transplant recipients with obstructive sleep apnea . J Heart Lung Transplant . 1997;16:394–397
- . Profound reflex bradycardia produced by transient hypoxia or hypercapnia in man . Eur Surg Res . 1977;9:75–84
- . Parasympathetic hyperresponsiveness and bradyarrhythmias during apnoea in hypertension . Clin Auton Res . 1992;2:171–176
- . Apnoea of prematurity . Paediatr Respir Rev . 2004;5(Suppl A):S377–S382
- . Cardiovascular responses to autonomic blockade in hypoxemic fetal lambs . Biol Neonate . 1980;37:233–242
- . The effect of fetal heart rate on cardiovascular function during hypoxemia . Am J Obstet Gynecol . 1980;138:1190–1199
- . Circulatory responses to acute hypoxia in spontaneously hypertensive and normotensive rats . Acta Physiol Pol . 1980;31:463–468
- . Effects on hypoxaemia on foetal heart rate, variability and cardiac rhythm . Clin Exp Pharmacol Physiol . 1998;25:577–584
- . Effect of acute hypoxemia and respiratory acidosis on the fetal heart rate in monkeys . Am J Obstet Gynecol . 1981;141:797–806
- . Hypoxic tachycardia in hypoxiaacclimated rats . Jpn J Physiol . 1982;32:149–152
- . Effects of hypoxia on cardiac vagal efferent activity and on the action of the vagus nerve at the heart in the dog . J Auton Nerv Syst . 1986;17:325–329
- . Abnormal heart rate response to hypercapnia in boys with an apparent life-threatening event . Acta Paediatr . 2002;91:1318–1323
- . Cardiovascular responses to hypoxia in the spontaneously breathing cat: reflexes originating from carotid and aortic bodies . Arch Biol Med Exp (Santiago) . 1983;16:29–41
- . Hypoxia inhibits baroreflex vagal bradycardia via a central action in anaesthetized rats . Exp Physiol . 1999;84:47–56
- . Abolition of hypoxic vagal bradycardia by lateral mesencephalic lesions in spinal cats . Am J Physiol . 1979;237:R15–R19
- . Failure of autoresuscitation in weanling mice: significance of cardiac glycogen and heart rate regulation . J Appl Physiol . 1999;87:203–210
- . The cardiorespiratory response to anoxia: normal development and the effect of nicotine . Respir Physiol . 1997;109:231–239
- . Sleep-induced apnea syndrome. Prevalence of cardiac arrhythmias and their re versal after tracheostomy . Am J Med . 1977;63:348–358
- . Nicotine and cotinine levels in pericardial fluid in victims of SIDS . Acta Paediatr . 1994;83:59–62
- . Cholinergic receptors in heart and brainstem of rats exposed to nicotine during development: implications for hypoxia tolerance and perinatal mortality . Brain Res Dev Brain Res . 1999;113:1–12
- . Impaired cardiac function during postnatal hypoxia in rats exposed to nicotine prenatally: implications for perinatal morbidity and mortality, and for sudden infant death syndrome . Teratology . 1997;55:177–184
- . The alpha4beta2 agonist SIB 1765F, but not the alpha7 agonist AR-R 17779, cross-sensitises to the psychostimulant effects of nicotine . Psychopharmacology (Berl) . 2000;150:233–236
- . Desensitization of the nicotine-induced mesolimbic dopamine responses during constant infusion with nicotine . Br J Pharmacol . 1995;114:454–460
- . The putative role of extra-synaptic mesolimbic dopamine in the neurobiology of nicotine dependence . Behav Brain Res . 2000;113:73–83
- . Chronic exposure to nicotine upregulates the human (alpha)4(beta)2 nicotinic acetylcholine receptor function . J Neurosci . 2001;21:1819–1829
- . Prenatal nicotine exposure alters the types of nicotinic receptors that facilitate excitatory inputs to cardiac vagal neurons . J Neurophysiol . 2004;92:2548–2554
- . Diversity of nicotinic acetylcholine receptors in rat hippocampal neurons. I. Pharmacological and functional evidence for distinct structural subtypes . J Pharmacol Exp Ther . 1993;265:1455–1473
- . Neural mechanisms generating respiratory pattern in mammalian brain stem-spinal cord in vitro. I. Spatiotemporal patterns of motor and medullary neuron activity . J Neurophysiol . 1990;64:1149–1169
- . Respiratory rhythm generation in the in vitro brain stem–spinal cord preparation of the neonatal rat . J Physiol . 1984;354:173–183
- Prenatal nicotine exposure increases apnoea and reduces nicotinic potentiation of hypoglossal inspiratory output in mice . J Physiol . 2002;538:957–973
- . Effect of nicotine exposure on postnatal ventilatory responses to hypoxia and hypercapnia . Respir Physiol . 1996;106:1–11
- . Deficient hypoxia awakening response in infants of smoking mothers: possible relationship to sudden infant death syndrome . J Pediatr . 1995;127:691–699
- . Respiratory plasticity: differential actions of continuous and episodic hypoxia and hypercapnia . Respir Physiol . 2001;129:25–35
- Invited review: intermittent hypoxia and respiratory plasticity . J Appl Physiol . 2001;90:2466–2475
- . Sleep apneas: an oxidative stress? . Am J Respir Crit Care Med . 2002;165:859–860
- . Increased injury following intermittent fetal hypoxia– reoxygenation is associated with increased free radical production in fetal rabbit brain . J Neuropathol Exp Neurol . 1999;58:972–981
- . Redox signaling in central neural regulation of cardiovascular function . Prog Biophys Mol Biol . 2004;84:125–149
- . Reactive oxygen species stimulate central and peripheral sympathetic nervous system activity . Am J Physiol Heart Circ Physiol . 2004;287:H695–H703
- . Tempol lowers blood pressure and sympathetic nerve activity but not vascular Oin DOCA-salt rats . Hypertension . 2004;43:329–334
- . Hydrogen peroxide increases the activity of rat sympathetic preganglionic neurons in vivo and in vitro . Neuroscience . 2003;121:641–647
- . Increased reactive oxygen species in rostral ventrolateral medulla contribute to neural mechanisms of hypertension in stroke-prone spontaneously hypertensive rats . Circulation . 2004;109:2357–2362
- . Altered production of nitric oxide and reactive oxygen species in rat nodose ganglion neurons during acute hypoxia . Brain Res . 2003;961:1–9
- . Optical imaging reveals elevated intracellular chloride in hippocampal pyramidal neurons after oxidative stress . J Neurosci . 1999;19:9209–9217
- . Iron toxicity in organotypic cultures of hippocampal slices: role of reactive oxygen species . J Neurochem . 2003;85:492–502
PII: S1016-3190(08)60001-4
doi:10.1016/S1016-3190(08)60001-4
© 2008 Buddhist Compassion Relief Tzu Chi Foundation. Published by Elsevier Inc. All rights reserved.
