Leptin signaling in the nucleus of the solitary tract alters the cardiovascular responses to activation of the chemoreceptor reflex
Abstract
Circulating levels of leptin are elevated in individuals suffering from chronic intermittent hypoxia (CIH). Systemic and central administration of leptin elicits increases in sympathetic nervous activity (SNA), arterial pressure (AP), and heart rate (HR), and it attenuates the baroreceptor reflex, cardiovascular responses that are similar to those observed during CIH as a result of activation of chemoreceptors by the systemic hypoxia. Therefore, experiments were done in anesthetized Wistar rats to investigate the effects of leptin in nucleus of the solitary tract (NTS) on AP and HR responses, and renal SNA (RSNA) responses during activation of NTS neurons and the chemoreceptor reflex. Microinjection of leptin (5–100 ng; 20 nl) into caudal NTS pressor sites (l-glutamate; l-Glu; 0.25 M; 10 nl) elicited dose-related increases in AP, HR, and RSNA. Leptin microinjections (5 ng; 20 nl) into these sites potentiated the increase in AP and HR elicited by l-Glu. Additionally, bilateral injections of leptin (5 ng; 100 nl) into NTS potentiated the increase in AP and attenuated the bradycardia to systemic activation of the chemoreflex. In the Zucker obese rat, leptin injections into NTS neither elicited cardiovascular responses nor altered the cardiovascular responses to activation of the chemoreflex. Taken together, these data indicate that leptin exerts a modulatory effect on neuronal circuits within NTS that control cardiovascular responses elicited during the reflex activation of arterial chemoreceptors and suggest that increased AP and SNA observed in individuals with CIH may be due, in part, by leptin's effects on the chemoreflex at the level of NTS.
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The mechanisms underlying central chemoreflex potentiation in obesity may be related to increased leptin production by adipocytes.
“The mechanisms that underlie central chemoreflex potentiation in obesity are unclear but may be related to increased leptin production by adipocytes187.”
From Obesity, kidney dysfunction and hypertension: mechanistic links (2019) · cites this paper as [187]
Cites
The Rat Brain in Stereotaxic Coordinates
Paxinos, G., & Watson, C. (1983) · Elsevier eBooks · doi:10.1016/c2009-0-63235-9 · Cited by 28,585 · see citing works
Central nervous system control of food intake
Schwartz, M. W., Woods, S. C., Porte, D., Seeley, R. J., & Baskin, D. G. (2000) · Nature · doi:10.1038/35007534 · Cited by 6,451 · see citing works
Pathophysiology of Sleep Apnea
Dempsey, J. A., Veasey, S. C., Morgan, B. J., & O'Donnell, C. P. (2010) · Physiological Reviews · doi:10.1152/physrev.00043.2008 · Cited by 2,243 · see citing works
Functional organization of central pathways regulating the cardiovascular system
Dampney, R. A. L. (1994) · Physiological Reviews · doi:10.1152/physrev.1994.74.2.323 · Cited by 1,648 · see citing works
Obstructive sleep apnoea and its cardiovascular consequences
Bradley, T. D., & Floras, J. S. (2009) · The Lancet · doi:10.1016/s0140-6736(08)61622-0 · Cited by 1,385 · see citing works
Leptin enters the brain by a saturable system independent of insulin
Banks, W. A., Kastin, A. J., Huang, W., Jaspan, J. B., & Maness, L. M. (1996) · Peptides · doi:10.1016/0196-9781(96)00025-3 · Cited by 1,222 · see citing works
Receptor-mediated regional sympathetic nerve activation by leptin.
Haynes, W. G., Morgan, D. A., Walsh, S. A., Mark, A. L., & Sivitz, W. I. (1997) · Journal of Clinical Investigation · doi:10.1172/jci119532 · Cited by 979 · see citing works
Obstructive sleep apnea as a cause of systemic hypertension. Evidence from a canine model.
Brooks, D., Horner, R. L., KOZAR, L. F., RENDER-TEIXEIRA, C. L., & Phillipson, E. A. (1997) · Journal of Clinical Investigation · doi:10.1172/jci119120 · Cited by 704 · see citing works
Leptin Activates Neurons in Ventrobasal Hypothalamus and Brainstem
Elmquist, J. K., Ahima, R. S., Maratos–Flier, E., Flier, J. S., & Saper, C. B. (1997) · Endocrinology · doi:10.1210/endo.138.2.5033 · Cited by 438 · see citing works
The central organization of carotid body afferent projections to the brainstem of the rat
Finley, J. C. W., & Katz, D. M. (1992) · Brain Research · doi:10.1016/0006-8993(92)90458-l · Cited by 436 · see citing works
Dunbar, J. C., Hu, Y., & Lu, H. (1997) · Diabetes · doi:10.2337/diab.46.12.2040 · Cited by 414 · see citing works
Evidence That the Caudal Brainstem Is a Target for the Inhibitory Effect of Leptin on Food Intake
Grill, H. J., Schwartz, M. W., Kaplan, J. M., Foxhall, J. S., Breininger, J., & Baskin, D. G. (2002) · Endocrinology · doi:10.1210/endo.143.1.8589 · Cited by 395 · cited 3× · see citing works
“However, leptin may also exert its effects directly within brain stem autonomic structures as leptin receptors have been identified in the caudal brain stem, especially within the dorsal vagal complex that includes NTS (29, 30, 36, 37, 42, 53, 68).”
BackgroundResultObesity hypertension: role of leptin and sympathetic nervous system
Hall, J. E. (2001) · American Journal of Hypertension · doi:10.1016/s0895-7061(01)02077-5 · Cited by 361 · see citing works
fer, H. S. A., Pauleit, D. O., Sudhop, T., Gouni‐Berthold, I., Ewig, S., & Berthold, H. K. (2002) · CHEST Journal · doi:10.1378/chest.122.3.829 · Cited by 357 · see citing works
Reconceptualizing Support Systems for Persons with Challenging Behaviors
Parette, H. P., Holt, J. M., & Smith, T. E. C. (1994) · Psychological Reports · doi:10.2466/pr0.1994.74.1.323 · Cited by 356 · see citing works
Function of the ventrolateral medulla in the control of the circulation
Ciriello, J., Caverson, M. M., & Polosa, C. (1986) · Brain Research Reviews · doi:10.1016/0165-0173(86)90005-6 · Cited by 331 · see citing works
Self-citationBrainstem projections of aortic baroreceptor afferent fibers in the rat
Ciriello, J. (1983) · Neuroscience Letters · doi:10.1016/0304-3940(83)90482-2 · Cited by 315 · see citing works
Self-citationLeptin and ghrelin levels in patients with obstructive sleep apnoea: effect of CPAP treatment
Harsch, I. A., Konturek, P. C., Koebnick, C., Kuehnlein, P. P., Fuchs, F. S., Schahin, S. P., Wiest, G. H., Hahn, E. G., Lohmann, T., & Ficker, J. H. (2003) · European Respiratory Journal · doi:10.1183/09031936.03.00010103 · Cited by 286 · see citing works
Immunohistochemical localization of leptin receptor in the rat brain
Shioda, S., Funahashi, H., Nakajo, S., Yada, T., Maruta, O., & Nakai, Y. (1998) · Neuroscience Letters · doi:10.1016/s0304-3940(98)00082-2 · Cited by 215 · see citing works
Differential Accessibility of Circulating Leptin to Individual Hypothalamic Sites
Faouzi, M., Leshan, R. L., Björnholm, M., Hennessey, T., Jones, J. C., & Münzberg, H. (2007) · Endocrinology · doi:10.1210/en.2007-0655 · Cited by 205 · see citing works
Brain Stem Is a Direct Target for Leptin’s Action in the Central Nervous System
Hosoi, T., Kawagishi, T., Okuma, Y., Tanaka, J., & Nomura, Y. (2002) · Endocrinology · doi:10.1210/en.2002-220077 · Cited by 205 · see citing works
Buyse, M., Ovesjö, M., Goïot, H., Guilmeau, S., Péranzi, G., Moizo, L., Walker, F., Lewin, M. J. M., Meister, B., & Bado, A. (2001) · European Journal of Neuroscience · doi:10.1046/j.0953-816x.2001.01628.x · Cited by 201 · see citing works
Erickson, J. T., & Millhorn, D. E. (1991) · Brain Research · doi:10.1016/0006-8993(91)91430-9 · Cited by 182 · see citing works
Hypothalamic Arcuate Nucleus Mediates the Sympathetic and Arterial Pressure Responses to Leptin
Rahmouni, K., & Morgan, D. A. (2006) · Hypertension · doi:10.1161/01.hyp.0000254827.59792.b2 · Cited by 180 · see citing works
Vardhan, A., Kachroo, A., & Sapru, H. N. (1993) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1993.264.1.r41 · Cited by 179 · see citing works
Localization of Leptin Receptor (Ob-R) Messenger Ribonucleic Acid in the Rodent Hindbrain
Mercer, J. G., Moar, K. M., & Hoggard, N. (1998) · Endocrinology · doi:10.1210/endo.139.1.5685 · Cited by 175 · see citing works
Leptin Directly Depolarizes Preproglucagon Neurons in the Nucleus Tractus Solitarius
Hisadome, K., Reimann, F. M., Gribble, F. M., & Trapp, S. (2010) · Diabetes · doi:10.2337/db10-0128 · Cited by 150 · see citing works
Leptin Transport Across the Blood-Brain Barrier: Implications for the Cause and Treatment of Obesity
Banks, W. A. (2001) · Current Pharmaceutical Design · doi:10.2174/1381612013398310 · Cited by 148 · see citing works
Tang‐Christensen, M., Havel, P. J., Jacobs, R. R., Larsen, P. J., & Cameron, J. L. (1999) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.84.2.5458 · Cited by 147 · see citing works
Leptin Acts in the Central Nervous System to Produce Dose-Dependent Changes in Arterial Pressure
Correia, M., Morgan, D. A., Sivitz, W. I., Mark, A. L., & Haynes, W. G. (2001) · Hypertension · doi:10.1161/01.hyp.37.3.936 · Cited by 146 · see citing works
Masked hypertension in obstructive sleep apnea syndrome
Baguet, J.-P., Levy, P. A., Barone‐Rochette, G., Tamisier, R., Pierre, H., Peeters, M. A., Mallion, J.-M., & Pépin, J. (2008) · Journal of Hypertension · doi:10.1097/hjh.0b013e3282f55049 · Cited by 146 · see citing works
Leptin Signaling in the Nucleus Tractus Solitarii Increases Sympathetic Nerve Activity to the Kidney
Mark, A. L., Agassandian, K., Morgan, D. A., Liu, X., Cassell, M. D., & Rahmouni, K. (2009) · Hypertension · doi:10.1161/hypertensionaha.108.124255 · Cited by 139 · see citing works
Ciriello, J., & Calaresu, F. R. (1983) · Journal of the Autonomic Nervous System · doi:10.1016/0165-1838(83)90110-8 · Cited by 138 · see citing works
Self-citationLeptin and the systems neuroscience of meal size control
Grill, H. J. (2009) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2009.10.005 · Cited by 137 · see citing works
Marsh, A. J., Fontes, M. A. P., Killinger, S., Pawlak, D. B., Polson, J. W., & Dampney, R. A. L. (2003) · Hypertension · doi:10.1161/01.hyp.0000090097.22678.0a · Cited by 136 · see citing works
Arterial chemoreceptor input to nucleus tractus solitarius
Mifflin, S. W. (1992) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1992.263.2.r368 · Cited by 136 · see citing works
Characterization of Leptin-Responsive Neurons in the Caudal Brainstem
Ellacott, K. L. J., Halatchev, I. G., & Cone, R. D. (2006) · Endocrinology · doi:10.1210/en.2005-0877 · Cited by 133 · see citing works
Expression of the leptin receptor in rat and human nodose ganglion neurones
Burdyga, G., Spiller, D. G., Morris, R., Lal, S., Thompson, D. G., Saeed, S. R., Dimaline, R., Varró, A., & Dockray, G. J. (2002) · Neuroscience · doi:10.1016/s0306-4522(01)00474-2 · Cited by 129 · see citing works
Central Nervous Integration of Cardiovascular Control
Spyer, K. M. (1982) · Journal of Experimental Biology · doi:10.1242/jeb.100.1.109 · Cited by 121 · see citing works
Chemosensory pathways in the brainstem controlling cardiorespiratory activity
Spyer, K. M., & Gourine, A. V. (2009) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2009.0082 · Cited by 118 · see citing works
White, D. P. (2006) · Proceedings of the American Thoracic Society · doi:10.1513/pats.200510-116jh · Cited by 118 · see citing works
Madden, C. J., & Morrison, S. F. (2005) · The Journal of Physiology · doi:10.1113/jphysiol.2005.086322 · Cited by 105 · see citing works
Chemoreceptor-sensitive neurons in commissural subnucleus of nucleus tractus solitarius of the rat
Chitravanshi, V. C., & Sapru, H. N. (1995) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1995.268.4.r851 · Cited by 99 · see citing works
Hypertension and obstructive sleep apnoea syndrome: current perspectives
Baguet, J.-P., Barone‐Rochette, G., & Pépin, J. (2009) · Journal of Human Hypertension · doi:10.1038/jhh.2008.147 · Cited by 96 · see citing works
Carotid chemoreflex. Neural pathways and transmitters.
Sapru, H. N. (1996) · PubMed · Cited by 93 · see citing works
Mechanisms mediating renal sympathetic activation to leptin in obesity
Morgan, D. A., Thedens, D. R., Weiss, R., & Rahmouni, K. (2008) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.90324.2008 · Cited by 89 · see citing works
Colombari, E., Menani, J. V., & Talman, W. T. (1996) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1996.270.6.r1220 · Cited by 86 · see citing works
Cardiovascular effects of leptin and orexins
Shirasaka, T., Takasaki, M., & Kannan, H. (2003) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00359.2002 · Cited by 82 · see citing works
Fos induction in central structures after afferent renal nerve stimulation
Solano-Flores, L. P., Rosas-Arellano, M. P., & Ciriello, J. (1997) · Brain Research · doi:10.1016/s0006-8993(96)01497-7 · Cited by 81 · see citing works
Self-citationRelationship between Obstructive Sleep Apnea and Diurnal Leptin Rhythms
Patel, S. R., Palmer, L. J., Larkin, E. K., Jenny, N. S., White, D. P., & Redline, S. S. (2004) · SLEEP · doi:10.1093/sleep/27.2.235 · Cited by 80 · see citing works
Sapru, H. N. (1996) · Advances in experimental medicine and biology · doi:10.1007/978-1-4615-5891-0_55 · Cited by 77 · see citing works
False-positive artifacts of tracer strategies distort autonomic connectivity maps
Fox, E. A., & Powley, T. L. (1989) · Brain Research Reviews · doi:10.1016/0165-0173(89)90009-x · Cited by 71 · see citing works
Leptin Impairs Cardiovagal Baroreflex Function at the Level of the Solitary Tract Nucleus
Arnold, A. C., Shaltout, H. A., Gallagher, P. E., & Diz, D. I. (2009) · Hypertension · doi:10.1161/hypertensionaha.109.138065 · Cited by 71 · see citing works
Leong, S. K., & Ling, E. (1990) · Journal of Neuroscience Methods · doi:10.1016/0165-0270(90)90067-p · Cited by 70 · see citing works
Chitravanshi, V. C., Kachroo, A., & Sapru, H. N. (1994) · Brain Research · doi:10.1016/0006-8993(94)90804-4 · Cited by 68 · see citing works
Leptin receptor expression in nodose ganglion cells projecting to the rat gastric fundus
Peiser, C., Springer, J., Groneberg, D. A., McGregor, G. P., Fischer, A., & Lang, R. E. (2002) · Neuroscience Letters · doi:10.1016/s0304-3940(02)00023-x · Cited by 63 · see citing works
Münzberg, H. (2008) · Physiology & Behavior · doi:10.1016/j.physbeh.2008.04.020 · Cited by 57 · see citing works
Calapai, G., Corica, F., Allegra, A., Corsonello, A., Sautebin, L., De Gregorio, T., Di Rosa, M., Costantino, G., Buemi, M., & Caputi, A. P. (1998) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0702121 · Cited by 56 · see citing works
Obstructive sleep apnea and hypertension
Narkiewicz, K., Wolf, J., López-Jiménez, F. A., & Somers, V. K. (2005) · Current Cardiology Reports · doi:10.1007/s11886-005-0061-z · Cited by 56 · see citing works
Respiratory responses to microinjections of leptin into the solitary tract nucleus
Inyushkin, A. N., Inyushkina, E. M., & Меркулова, Н. А. (2009) · Neuroscience and Behavioral Physiology · doi:10.1007/s11055-009-9124-8 · Cited by 55 · see citing works
Cruz, J. C., Bonagamba, L. G. H., Machado, B. H., et al. (2008) · Neuroscience · doi:10.1016/j.neuroscience.2008.08.070 · Cited by 45 · see citing works
Messenger, S. A., Moreau, J. M., & Ciriello, J. (2012) · Brain Research · doi:10.1016/j.brainres.2012.01.074 · Cited by 41 · see citing works
Self-citationMechanisms of the Respiratory Activity of Leptin at the Level of the Solitary Tract Nucleus
Михайловна, И. Е., Меркулова, Н. А., & Inyushkin, A. N. (2010) · Neuroscience and Behavioral Physiology · doi:10.1007/s11055-010-9316-2 · Cited by 40 · see citing works
Yuan, C.-S., Attele, A. S., Dey, L., et al. (2000) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)38884-6 · Cited by 40 · see citing works
Gao, L., Pan, Y.-X., Wang, W.-Z., et al. (2006) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00681.2006 · Cited by 39 · see citing works
Cardiovascular depressor responses to stimulation of substantia nigra and ventral tegmental area
Kirouac, G. J., & Ciriello, J. (1997) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.1997.273.6.h2549 · Cited by 32 · see citing works
Self-citationMuzzin, P., Cusin, I., Charnay, Y., & Rohner-Jeanrenaud, F. (2000) · Regulatory Peptides · doi:10.1016/s0167-0115(00)00150-6 · Cited by 29 · see citing works
Medullary pathways mediating the parasubthalamic nucleus depressor response
Ciriello, J., Solano-Flores, L. P., Rosas-Arellano, M. P., Kirouac, G. J., & Babic, T. (2008) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00437.2007 · Cited by 29 · see citing works
Self-citationFos expression in the NTS in response to peripheral chemoreflex activation in awake rats
Cruz, J. C., Bonagamba, L. G. H., Stern, J. E., et al. (2009) · Autonomic Neuroscience · doi:10.1016/j.autneu.2009.08.016 · Cited by 26 · see citing works
The Role of the Vagus Nerve in Mediating the Long‐Term Anorectic Effects of Leptin
Sachot, C., Rummel, C. D., Bristow, A. F., & Luheshi, G. N. (2007) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2006.01528.x · Cited by 25 · see citing works
Gastric Effects of Galanin and Its Interaction with Leptin on Brainstem Neuronal Activity
Yuan, C., Dey, L., Xie, J., et al. (2002) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.301.2.488 · Cited by 21 · see citing works
Sleep Apnea and Cardiovascular Disease
Logan, A. G., & Bradley, T. D. (2010) · Current Hypertension Reports · doi:10.1007/s11906-010-0107-5 · Cited by 19 · see citing works
Geometry of rubrospinal, rubroolivary, and local circuit neurons in the macaque red nucleus
Burman, K. J., Darian‐Smith, C., & Darian-Smith, I. (2000) · The Journal of Comparative Neurology · doi:10.1002/1096-9861(20000724)423:2 · Cited by 16 · see citing works
Cruz, J. C., & Machado, B. H. (2009) · Autonomic Neuroscience · doi:10.1016/j.autneu.2008.11.011 · Cited by 11 · see citing works
Linkage of serum leptin levels in families with sleep apnea
Larkin, E. K., Elston, R. C., Patel, S. R., et al. (2004) · International Journal of Obesity · doi:10.1038/sj.ijo.0802872 · Cited by 9 · see citing works
An anomalous vagorenal reflex pathway in the cat
Calaresu, F. R., Knuepfer, M. M., Ciriello, J., et al. (1985) · Experimental Neurology · doi:10.1016/0014-4886(85)90218-3 · Cited by 5 · see citing works
Self-citationLemus, M., Montero, S., Luquı́n, S., et al. (2009) · Advances in experimental medicine and biology · doi:10.1007/978-90-481-2259-2_46 · Cited by 4 · see citing works
Elmquist (1998) · doi:10.1002/(sici)1096-9861(19980615)395:4
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Mark, A. L. (2013) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00180.2013 · Cited by 162 · see citing works
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- Authors
- Ciriello, J., & Moreau, J. M.
- Affiliations
- Western University (CA)
- Corresponding author
- Ciriello, John
- ORCID
- Ciriello, John
- Venue
- American Journal of Physiology-Regulatory, Integrative and Comparative Physiology
- Publisher
- American Physiological Society
- Published
- 2012-10-01
- Volume
- 303
- Issue
- 7
- Pages
- R727-R736
- ISSN
- 0363-6119 (ISSN-L)
- 1522-1490
- OpenAlex
- W2164990671
- Cited by
- 33
- References
- 78
- Citations by year
- 2024: 2 · 2022: 3 · 2020: 3 · 2019: 1 · 2018: 1 · 2016: 3 · 2015: 6 · 2014: 5 · 2013: 7 · 2012: 2
- FWCI
- 2.82
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Regulatory, Integrative and Comparative Physiology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroscience of respiration and sleep
- Health Sciences › Medicine › Physiology › Obstructive Sleep Apnea Research
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
- Keywords
- leptin, nucleus tractus solitarius, chemoreceptor reflex, chronic intermittent hypoxia, arterial pressure, heart rate, renal sympathetic nerve activity, sympathetic activity, baroreflex, Zucker fatty rats, leptin resistance
- MeSH terms
- Animals, Blood Pressure, Chemoreceptor Cells, Disease Models, Animal, Heart Rate, Male, Microinjections, Obesity, Rats, Zucker, Signal Transduction, Rats, Wistar, Solitary Nucleus, Baroreflex, Glutamic Acid, Leptin, Rats, Receptors, Leptin
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