Neurochemical alterations of intrinsic cardiac ganglionated nerve plexus caused by arterial hypertension developed during ageing in spontaneously hypertensive and Wistar Kyoto rats.
CGRP
ChAT
SIF cells
TH
heart ganglia, nerves and plexus
hypertension
immunohistochemistry
Journal
Journal of anatomy
ISSN: 1469-7580
Titre abrégé: J Anat
Pays: England
ID NLM: 0137162
Informations de publication
Date de publication:
10 2023
10 2023
Historique:
revised:
28
03
2023
received:
06
01
2023
accepted:
30
03
2023
pmc-release:
21
04
2025
medline:
11
9
2023
pubmed:
21
4
2023
entrez:
21
04
2023
Statut:
ppublish
Résumé
The acknowledged hypothesis of the cause of arterial hypertension is the emerging disbalance in sympathetic and parasympathetic regulations of the cardiovascular system. This disbalance manifests in a disorder of sustainability of endogenous autonomic and sensory neural substances including calcitonin gene-related peptide (CGRP). This study aimed to examine neurochemical alterations of intrinsic cardiac ganglionated nerve plexus (GP) triggered by arterial hypertension during ageing in spontaneously hypertensive rats of juvenile (prehypertensive, 8-9 weeks), adult (early hypertensive, 12-18 weeks) and elderly (persistent hypertensive, 46-60 weeks) age in comparison with the age-matched Wistar-Kyoto rats as controls. Parasympathetic, sympathetic and sensory neural structures of GP were analysed and evaluated morphometrically in tissue sections and whole-mount cardiac preparations. Both the elevated blood pressure and the evident ultrasonic signs of heart failure were identified for spontaneously hypertensive rats and in part for the aged control rats. The amount of adrenergic and immunoreactive to CGRP neural structures was increased in the adult group of spontaneously hypertensive rats along with the significant alterations that occurred during ageing. In conclusion, the revealed chemical alterations of GP support the hypothesis about the possible disbalance of efferent and afferent heart innervation and may be considered as the basis for the emergence and progression of arterial hypertension and perhaps even as a consequence of hypertension in the aged spontaneously hypertensive rats. The determined anatomical changes in the ageing Wistar-Kyoto rats suggest this breed being as inappropriate for its use as control animals for hypertension studies in older animal age.
Identifiants
pubmed: 37083051
doi: 10.1111/joa.13877
pmc: PMC10485580
doi:
Substances chimiques
Calcitonin Gene-Related Peptide
JHB2QIZ69Z
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
630-647Informations de copyright
© 2023 Anatomical Society.
Références
Adams, M.A., Bobik, A. & Korner, P.I. (1989) Differential development of vascular and cardiac hypertrophy in genetic hypertension. Relation to sympathetic function. Hypertension (Dallas, Tex: 1979), 14(2), 191-202.
Aksu, T., Gopinathannair, R., Gupta, D. & Pauza, D.H. (2021) Intrinsic cardiac autonomic nervous system: what do clinical electrophysiologists need to know about the “heart brain”? Journal of Cardiovascular Electrophysiology, 32(6), 1737-1747.
Aksu, T., Gupta, D. & Pauza, D.H. (2021) Anatomy and physiology of intrinsic cardiac autonomic nervous system: da Vinci anatomy card #2. Case Reports, 3(4), 625-629.
Ashton, J.L., Argent, L., Smith, J.E.G., Jin, S., Sands, G.B., Smaill, B.H. et al. (2020) Evidence of structural and functional plasticity occurring within the intracardiac nervous system of spontaneously hypertensive rats. American Journal of Physiology. Heart and Circulatory Physiology, 318(6), H1387-H1400.
Atanasova, D.Y., Iliev, M.E. & Lazarov, N.E. (2011) Morphology of the rat carotid body. Biomedical Reviews, 22, 41-55.
Bergdahl, A., Valdemarsson, S., Nilsson, T., Sun, X.Y., Hedner, T. & Edvinsson, L. (1999) Dilatory responses to acetylcholine, calcitonin gene-related peptide and substance P in the congestive heart failure rat. Acta Physiologica Scandinavica, 165(1), 15-23.
Boluyt, M.O., Bing, O.H. & Lakatta, E.G. (1995) The ageing spontaneously hypertensive rat as a model of the transition from stable compensated hypertrophy to heart failure. European Heart Journal, 16(Suppl N), 19-30.
Brain, S.D., Williams, T.J., Tippins, J.R., Morris, H.R. & MacIntyre, I. (1985) Calcitonin gene-related peptide is a potent vasodilator. Nature, 313(5997), 54-56.
Chiba, T., Black, A.C. & Williams, T.H. (1977) Evidence for dopamine-storing interneurons and paraneurons in rhesus monkey sympathetic ganglia. Journal of Neurocytology, 6, 441-453.
de Rezende, L.M.T., Soares, L.L., Drummond, F.R., Suarez, P.Z., Leite, L., Rodrigues, J.A. et al. (2021) Is the Wistar rat a more suitable normotensive control for SHR to test blood pressure and cardiac structure and function? International Journal of Cardiovascular Sciences, 35(2), 161-167.
Doggrell, S.A. & Brown, L. (1998) Rat models of hypertension, cardiac hypertrophy and failure. Cardiovascular Research, 39(1), 89-105.
Drazner, M.H. (2011) The progression of hypertensive heart disease. Circulation, 123(3), 327-334.
Escott, K.J. & Brain, S.D. (1993) Effect of a calcitonin gene-related peptide antagonist (CGRP8-37) on skin vasodilatation and oedema induced by stimulation of the rat saphenous nerve. British Journal of Pharmacology, 110(2), 772-776.
Felippe, I.S.A., Zera, T., da Silva, M.P., Moraes, D.J.A., McBryde, F. & Paton, J.F.R. (2022) The sympathetic nervous system exacerbates carotid body sensitivity in hypertension. Cardiovascular Research, 119(1), 316-331.
Fisher, J.P. & Paton, J.F.R. (2011) The sympathetic nervous system and blood pressure in humans: implications for hypertension. Journal of Human Hypertension, 26(8), 463-475.
GBD 2019 Risk Factors Collaborators. (2020) Global burden of 87 risk factors in 204 countries and territories, 1990-2019: a systematic analysis for the global burden of disease study 2019. Lancet (London, England), 396(10258), 1223-1249.
Grassi, G. & Ram, V.S. (2016) Evidence for a critical role of the sympathetic nervous system in hypertension. Journal of the American Society of Hypertension, 10(5), 457-466.
Hanna, P., Dacey, M.J., Brennan, J., Moss, A., Robbins, S., Achanta, S. et al. (2021) Innervation and neuronal control of the mammalian sinoatrial node a comprehensive atlas. Circulation Research, 128(9), 1279-1296.
Herring, N., Lee, C.W., Sunderland, N., Wright, K. & Paterson, D.J. (2011) Pravastatin normalises peripheral cardiac sympathetic hyperactivity in the spontaneously hypertensive rat. Journal of Molecular and Cellular Cardiology, 50(1), 99-106.
Hoard, J.L., Hoover, D.B., Mabe, A.M., Blakely, R.D., Feng, N. & Paolocci, N. (2008) Cholinergic neurons of mouse intrinsic cardiac ganglia contain noradrenergic enzymes, norepinephrine transporters, and the neurotrophin receptors tropomyosin-related kinase a and p75. Neuroscience, 156(1), 129-142.
Hoover, D.B., Isaacs, E.R., Jacques, F., Hoard, J.L., Pagé, P. & Armour, J.A. (2009) Localization of multiple neurotransmitters in surgically derived specimens of human atrial ganglia. Neuroscience, 164(3), 1170-1179.
Horn, J.P. & Stofer, W.D. (1989) Preganglionic and sensory origins of calcitonin gene-related peptide-like and substance P-like immunoreactivities in bullfrog sympathetic ganglia. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience, 9(7), 2543-2561.
Hoshi, H., Sakagami, H., Owada, Y. & Kondo, H. (2006) Localization of Ca/calmodulin-dependent protein kinase I in the carotid body chief cells and the ganglionic small intensely fluorescent (SIF) cells of adult rats. Advances in Experimental Medicine and Biology, 580, 87-92.
Huang, S.M., Wu, Y.L., Peng, S.L., Peng, H.H., Huang, T.Y., Ho, K.C. et al. (2016) Inter-strain differences in default mode network: a resting state FMRI study on spontaneously hypertensive rat and Wistar Kyoto rat. Scientific Reports, 6, 21697.
Kajekar, R. & Myers, A.C. (2008) Calcitonin gene-related peptide affects synaptic and membrane properties of bronchial parasympathetic neurons. Respiratory Physiology & Neurobiology, 160(1), 28-36.
Kanazawa, H., Ieda, M., Kimura, K., Arai, T., Kawaguchi-Manabe, H., Matsuhashi, T. et al. (2010) Heart failure causes cholinergic transdifferentiation of cardiac sympathetic nerves via gp130-signaling cytokines in rodents. The Journal of Clinical Investigation, 120(2), 408-421.
Kee, Z., Kodji, X. & Brain, S.D. (2018) The role of calcitonin gene related peptide (CGRP) in neurogenic vasodilation and its cardioprotective effects. Frontiers in Physiology, 9, 1249.
Kondo, M., Terada, M., Fujiwara, T., Arita, N., Yano, A. & Tabei, R. (1995) Noradrenergic hyperinnervation in the heart of stroke-prone spontaneously hypertensive rats. Clinical and Experimental Pharmacology & Physiology, 22(1), S75-S76.
Kumar, A., Potts, J.D. & DiPette, D.J. (2019) Protective role of α-calcitonin gene-related peptide in cardiovascular diseases. Frontiers in Physiology, 10, 821.
Kurtz, T.W. & Curtis Morris, R. (1987) Biological variability in Wistar-Kyoto rats. Implications for research with the spontaneously hypertensive rat. Hypertension, 10(1), 127-131.
Kurtz, T.W., Montano, M., Chan, L. & Kabra, P. (1989) Molecular evidence of genetic heterogeneity in Wistar-Kyoto rats: implications for research with the spontaneously hypertensive rat. Hypertension, 13(2), 188-192.
Larsen, H.E., Lefkimmiatis, K. & Paterson, D.J. (2016) Sympathetic neurons are a powerful driver of myocyte function in cardiovascular disease. Scientific Reports, 6, 38898.
LeGrice, I.J., Pope, A.J., Sands, G.B., Whalley, G., Doughty, R.N. & Smaill, B.H. (2012) Progression of myocardial remodeling and mechanical dysfunction in the spontaneously hypertensive rat. American Journal of Physiology. Heart and Circulatory Physiology, 303(11), H1353-H1365.
Lerman, L.O., Kurtz, T.W., Touyz, R.M., Ellison, D.H., Chade, A.R., Crowley, S.D. et al. (2019) Animal models of hypertension: a scientific statement from the American Heart Association. Hypertension, 73(6), 87-120.
Li, D., Lee, C.W., Buckler, K., Parekh, A., Herring, N. & Paterson, D.J. (2012) Abnormal intracellular calcium homeostasis in sympathetic neurons from young prehypertensive rats. Hypertension, 59(3), 642-649.
Li, L., Hatcher, J.T., Hoover, D.B., Gu, H., Wurster, R.D. & Cheng, Z.J. (2014) Distribution and morphology of calcitonin gene-related peptide and substance P immunoreactive axons in the whole-mount atria of mice. Autonomic Neuroscience: Basic and Clinical, 181(1), 37-48.
Mancia, G. & Grassi, G. (2014) The autonomic nervous system and hypertension. Circulation Research, 114(11), 1804-1814.
Masuda, Y. (2000) Role of the parasympathetic nervous system and interaction with the sympathetic nervous system in the early phase of hypertension. Journal of Cardiovascular Pharmacology, 36(Suppl 2), S61-S64.
Navickaite, I., Pauziene, N. & Pauza, D.H. (2021) Anatomical evidence of non-parasympathetic cardiac nitrergic nerve fibres in rat. Journal of Anatomy, 238(1), 20-35.
N'Diaye, A., Gannesen, A., Borrel, V., Maillot, O., Enault, J., Racine, P.J. et al. (2017) Substance P and calcitonin gene-related peptide: key regulators of cutaneous microbiota homeostasis. Frontiers in Endocrinology, 8, 15.
Okamoto, K. & Aoki, K. (1963) Development of a strain of spontaneously hypertensive rats. Japanese Circulation Journal, 27(3), 282-293.
Panzenhagen, A.C., Bau, C.H.D., Grevet, E.H. & Rovaris, D.L. (2019) An animal model of what? The case of spontaneously hypertensive rats. Progress in Neuro-Psychopharmacology & Biological Psychiatry, 94, 109617.
Parsons, R.L. (2004) Mammalian cardiac ganglia as local integration centers: histochemical and electrophysiological evidence. In: Dun, N.J., Machado, B.H. & Pilowsky, P.M. (Eds.) Neural Mechanisms of Cardiovascular Regulation. Boston: Springer, pp. 335-356.
Patterson, P.H. (1978) Environmental determination of autonomic neurotransmitter functions. Annual Review of Neuroscience, 1, 1-17.
Pauza, D.H., Pauziene, N., Pakeltyte, G. & Stropus, R. (2002) Comparative quantitative study of the intrinsic cardiac ganglia and neurons in the rat, Guinea pig, dog and human as revealed by histochemical staining for acetylcholinesterase. Annals of Anatomy, 184(2), 125-136.
Pauza, D. H., Rysevaite-Kyguoliene, K., Vismantaite, J., Brack, K. E., Inokaitis, H., Pauza, A. G. et al. (2014) A combined acetylcholinesterase and immunohistochemical method for precise anatomical analysis of intrinsic cardiac neural structures. Annals of Anatomy, 196(6), 430-440.
Pauza, D.H., Skripka, V., Pauziene, N. & Stropus, R. (2000) Morphology, distribution, and variability of the epicardiac neural ganglionated subplexuses in the human heart. The Anatomical Record, 259(4), 353-382.
Pauziene, N., Alaburda, P., Rysevaite-Kyguoliene, K., Pauza, A.G., Inokaitis, H., Masaityte, A. et al. (2016) Innervation of the rabbit cardiac ventricles. Journal of Anatomy, 228(1), 26-46.
Pauziene, N., Ranceviene, D., Rysevaite-Kyguoliene, K., Inokaitis, H., Saburkina, I., Plekhanova, K. et al. (2022) Comparative analysis of intracardiac neural structures in the aged rats with essential hypertension. Anatomical Record. Available from: https://doi.org/10.1002/ar.25109 Online ahead of print.
Pauziene, N., Rysevaite-Kyguoliene, K., Alaburda, P., Pauza, A.G., Skukauskaite, M., Masaityte, A. et al. (2017) Neuroanatomy of the pig cardiac ventricles. A stereomicroscopic, confocal and electron microscope study. Anatomical Record, 300(10), 1756-1780.
Purves, D. (Ed.). (2001) The Visceral Motor System. In: Neuroscience, 2nd edition, Sunderland: Sinauer Associates.
Ranceviene, D., Rysevaite-Kyguoliene, K., Inokaitis, H., Saburkina, I., Plekhanova, K., Sabeckiene, D. et al. (2022) Early structural alterations of intrinsic cardiac ganglionated plexus in spontaneously hypertensive rats. Histology and Histopathology, 37(10), 955-970.
Reckelhoff, J.F., Yanes Cardozo, L.L. & Fortepiani, M.L.A. (2018) Models of hypertension in aging. In: Conn's Handbook of Models for Human Aging. Oxford: Elsevier, 703-720.
Richardson, R.J., Grkovic, I. & Anderson, C.R. (2003) Immunohistochemical analysis of intracardiac ganglia of the rat heart. Cell and Tissue Research, 314(3), 337-350.
Russell, F.A., King, R., Smillie, S.J., Kodji, X. & Brain, S.D. (2014) Calcitonin gene-related peptide: physiology and pathophysiology. Physiological Reviews, 94(4), 1099-1142.
Rysevaite, K., Saburkina, I., Pauziene, N., Vaitkevicius, R., Noujaim, S.F., Jalife, J. et al. (2011) Immunohistochemical characterization of the intrinsic cardiac neural plexus in whole-mount mouse heart preparations. Heart Rhythm, 8(5), 731-738.
Sahn, D.J., Demaria, A., Kisslo, J. & Weyman, A. (1978) Recommendations regarding quantitation in M-mode echocardiography: results of a survey of echocardiographic measurements. Circulation, 58(6), 1072-1083.
Santos, M. & Shah, A.M. (2014) Alterations in cardiac structure and function in hypertension. Current Hypertension Reports, 16(5), 428.
Schindelin, J., Arganda-Carreras, I., Frise, E., Kaynig, V., Longair, M., Pietzsch, T. et al. (2012) Fiji: an open-source platform for biological-image analysis. Nature Methods, 9(7), 676-682.
Sengupta, P. (2013) The laboratory rat: relating its age with human's. International Journal of Preventive Medicine, 4(6), 624-630.
Shanks, J., Mane, S., Ryan, R. & Paterson, D.J. (2013) Ganglion-specific impairment of the norepinephrine transporter in the hypertensive rat. Hypertension, 61(1), 187-193.
Shanks, J., Manou-Stathopoulou, S., Lu, C.J., Li, D., Paterson, D.J. & Herring, N. (2013) Cardiac sympathetic dysfunction in the prehypertensive spontaneously hypertensive rat. American Journal of Physiology. Heart and Circulatory Physiology, 305(7), H980-H986.
Shivkumar, K., Ajijola, O.A., Anand, I., Armour, J.A., Chen, P.S., Esler, M. et al. (2016) Clinical neurocardiology defining the value of neuroscience-based cardiovascular therapeutics. The Journal of Physiology, 594(14), 3911-3954.
Singhal, P., Senecal, J.M.M. & Nagy, J.I. (2023) Expression of the gap junction protein connexin36 in small intensely fluorescent (SIF) cells in cardiac parasympathetic ganglia of rodents. Neuroscience Letters, 793, 136989.
Slama, M., Ahn, J., Varagic, J., Susic, D. & Frohlich, E.D. (2004) Long-term left ventricular echocardiographic follow-up of SHR and WKY rats: effects of hypertension and age. American Journal of Physiology. Heart and Circulatory Physiology, 286, 181-185.
Smillie, S.J. & Brain, S.D. (2011) Calcitonin gene-related peptide (CGRP) and its role in hypertension. Neuropeptides, 45(2), 93-104.
Smith, D.I., Tran, H.T. & Poku, J. (2018) Hemodynamic considerations in the pathophysiology of peripheral neuropathy. Current Research in Diabetes & Obesity Journal, 5(5), 92-97.
Supowit, S.C., Zhao, H. & DiPette, D.J. (2001) Nerve growth factor enhances calcitonin gene-related peptide expression in the spontaneously hypertensive rat. Hypertension, 37(2 Pt 2), 728-732.
Tomas, R., Kristina, R.K., Neringa, P., Hermanas, I. & Dainius, P.H. (2022) Intrinsic cardiac neurons of the adult pigs: chemical types, abundance, parameters and distribution within ganglionated plexus. Annals of Anatomy, 243, 151935.
Toyoda, K., Faraci, F.M., Russo, A.F., Davidson, B.L. & Heistad, D.D. (2000) Gene transfer of calcitonin gene-related peptide to cerebral arteries. American Journal of Physiology. Heart and Circulatory Physiology, 278(2), H586-H594.
Valensi, P. (2021) Autonomic nervous system activity changes in patients with hypertension and overweight: role and therapeutic implications. Cardiovascular Diabetology, 20(1), 170.
van Zwieten, P.A., Hendriks, M.G.C., Pfaffendorf, M., Bruning, T.A. & Chang, P.C. (1995) The parasympathetic system and its muscarinic receptors in hypertensive disease. Journal of Hypertension, 13(10), 1079-1090.
Watson, L.E., Sheth, M., Denyer, R.F. & Dostal, D.E. (2004) Baseline echocardiographic values for adult male rats. Journal of the American Society of Echocardiography, 17(2), 161-167.
Weight, F.F. & Weitsen, H.A. (1977) Identification of small intensely fluorescent (SIF) cells as chromaffin cells in bullfrog sympathetic ganglia. Brain Research, 128(2), 213-226.
Weihe, E., Schütz, B., Hartschuh, W., Anlauf, M., Schäfer, M.K. & Eiden, L.E. (2005) Coexpression of cholinergic and noradrenergic phenotypes in human and nonhuman autonomic nervous system. The Journal of Comparative Neurology, 492(3), 370-379.
White, C.R. & Seymour, R.S. (2013) The role of gravity in the evolution of mammalian blood pressure. Evolution, 68, 901-908.
Yokoyama, T., Saito, H., Nakamuta, N. & Yamamoto, Y. (2022) Immunohistochemical localization of vesicular nucleotide transporter in small intensely fluorescent (SIF) cells of the rat superior cervical ganglion. Tissue & Cell, 79, 101924.
Zhang-James, Y., Middleton, F.A. & Faraone, S.v. (2013) Genetic architecture of Wistar-Kyoto rat and spontaneously hypertensive rat substrains from different sources. Physiological Genomics, 45(13), 528-538.
Zhou, Z.H., Peng, J., Ye, F., Li, N.S., Deng, H.W. & Li, Y.J. (2002) Delayed cardioprotection induced by nitroglycerin is mediated by alpha-calcitonin gene-related peptide. Naunyn-Schmiedeberg's Archives of Pharmacology, 365(4), 253-259.
Zugck, C., Lossnitzer, D., Backs, J., Kristen, A., Kinscherf, R. & Haass, M. (2003) Increased cardiac norepinephrine release in spontaneously hypertensive rats: role of presynaptic alpha-2A adrenoceptors. Journal of Hypertension, 21(7), 1363-1369.