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Cardiovascular & Hematological Agents in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1871-5257
ISSN (Online): 1875-6182

Research Article

Subthreshold Doses of Inflammatory Mediators potentiate One Another to Elicit Reflex Cardiorespiratory Responses in Anesthetized Rats

Author(s): Ravindran Revand, Sanjeev K. Singh* and Madaswamy S. Muthu

Volume 22, Issue 1, 2024

Published on: 10 May, 2023

Page: [90 - 99] Pages: 10

DOI: 10.2174/1871525721666230407103734

Price: $65

Abstract

Background: Reflex cardio-vascular and respiratory (CVR) alterations evoked by intraarterial instillation of nociceptive agents are termed vasosensory reflexes. Such responses elicited by optimal doses of inflammatory mediators have been described in our earlier work.

Objective: The present study was designed to evaluate the interactions between subthreshold doses of inflammatory mediators on perivascular nociceptive afferents in urethane anesthetized rats.

Methods: Healthy male adult rats (Charles-Foster strain) were anesthetized with an intraperitoneal injection of urethane. After anesthesia, the right femoral artery was cannulated. Respiratory movements, blood pressure, and electrocardiogram were recorded. The interactions between subthreshold doses of algogens in the elicitation of vasosensory reflex responses were studied by instillation of bradykinin (1 nM) and histamine (100 μM) into the femoral artery one after the other, in either temporal combination in separate groups of rats. The CVR responses obtained in these groups were then compared with the responses produced by 100 μM histamine and 1 nM bradykinin in saline-pretreated groups, which served as control.

Results: Subthreshold doses of histamine elicited transient tachypnoeic, hyperventilatory, hypotensive, and bradycardiac responses, in rats pretreated with subthreshold doses of bradykinin [p < 0.01, two-sided Dunnett’s test] but not in saline pretreated groups [p > 0.05, two-sided Dunnett’s test]. Similar responses were elicited by bradykinin after histamine pretreatment compared to the saline-pretreated group. Furthermore, CVR responses produced by histamine in the bradykininpretreated group were greater in magnitude as compared to bradykinin-induced responses in the histamine-pretreated group [p < 0.05, two-sided Dunnett’s test].

Conclusion: The present study demonstrates that both bradykinin and histamine potentiate one another in the elicitation of vasosensory reflex responses, and bradykinin is a better potentiator than histamine at the level of perivascular nociceptive afferents in producing reflex CVR changes.

Keywords: Bradykinin, histamine, potentiation, subthreshold, vasosensory reflexes, nociception, algogens, perivascular.

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[1]
Fitzcharles, M.A.; Cohen, S.P.; Clauw, D.J.; Littlejohn, G.; Usui, C.; Häuser, W. Nociplastic pain: towards an understanding of prevalent pain conditions. Lancet, 2021, 397(10289), 2098-2110.
[http://dx.doi.org/10.1016/S0140-6736(21)00392-5] [PMID: 34062144]
[2]
Rosa, A.C.; Fantozzi, R. The role of histamine in neurogenic inflammation. Br. J. Pharmacol., 2013, 170(1), 38-45.
[http://dx.doi.org/10.1111/bph.12266] [PMID: 23734637]
[3]
Moore, J.P.; Hainsworth, R.; Drinkhill, M.J. Reflexes from pulmonary arterial baroreceptors in dogs: Interaction with carotid sinus baroreceptors. J. Physiol., 2011, 589(16), 4041-4052.
[http://dx.doi.org/10.1113/jphysiol.2011.210732] [PMID: 21690195]
[4]
McQueen, D.S.; Bond, S.M.; Moores, C.; Chessell, I.; Humphrey, P.P.A.; Dowd, E. Activation of P2X receptors for adenosine triphosphate evokes cardiorespiratory reflexes in anaesthetized rats. J. Physiol., 1998, 507(3), 843-855.
[http://dx.doi.org/10.1111/j.1469-7793.1998.843bs.x] [PMID: 9508844]
[5]
Smith, P.J.W.; McQueen, D.S. Anandamide induces cardiovascular and respiratory reflexes via vasosensory nerves in the anaesthetized rat. Br. J. Pharmacol., 2001, 134(3), 655-663.
[http://dx.doi.org/10.1038/sj.bjp.0704296] [PMID: 11588121]
[6]
Smith, P.J.W.; McQueen, D.S. Perivascular nerves induce cardiorespiratory reflexes in response to algogens in anaesthetised rats. Neurosci. Res., 2004, 50(3), 271-281.
[http://dx.doi.org/10.1016/j.neures.2004.07.006] [PMID: 15488290]
[7]
Singh, S.K.; Mandal, M.B.; Ravindran, R. Instillation of bradykinin into femoral artery elicits cardiorespiratory reflexes involving perivascular afferents in anesthetized rats. Physiol. Int., 2020, 107(1), 40-54.
[http://dx.doi.org/10.1556/2060.2020.00009] [PMID: 32491287]
[8]
Singh, S.K.; Muthu, M.S.; Revand, R.; Mandal, M.B. Intra-arterial instillation of a nociceptive agent modulates cardiorespiratory parameters involving 5-HT3 and TRPV1 receptors in anesthetized rats. Cardiovasc. Hematol. Disord. Drug Targets, 2021, 21(1), 46-54.
[http://dx.doi.org/10.2174/1871529X21666210408101442] [PMID: 33829976]
[9]
Revand, R.; Singh, S.K. Retrograde cannulation of femoral artery: A novel experimental design for precise elicitation of vasosensory reflexes in anesthetized rats. MethodsX, 2020, 7, 101017.
[http://dx.doi.org/10.1016/j.mex.2020.101017] [PMID: 32793432]
[10]
Revand, R.; Singh, S.K. Ipsilateral somatic nerves mediate histamine-induced vasosensory reflex responses involving perivascular afferents in rat models. Sci. Rep., 2021, 11(1), 14648.
[http://dx.doi.org/10.1038/s41598-021-94110-x] [PMID: 34282171]
[11]
Foreman, R.D.; Garrett, K.M.; Blair, R.W. Mechanisms of cardiac pain. Compr. Physiol., 2015, 5(2), 929-960.
[http://dx.doi.org/10.1002/cphy.c140032] [PMID: 25880519]
[12]
Chandler, M.J.; Zhang, J.; Qin, C.; Yuan, Y.; Foreman, R.D. Intrapericardiac injections of algogenic chemicals excite primate C1-C2 spinothalamic tract neurons. Am. J. Physiol. Regul. Integr. Comp. Physiol., 2000, 279(2), R560-R568.
[http://dx.doi.org/10.1152/ajpregu.2000.279.2.R560] [PMID: 10938246]
[13]
Julius, D.; Basbaum, A.I. Molecular mechanisms of nociception. Nature, 2001, 413(6852), 203-210.
[http://dx.doi.org/10.1038/35093019] [PMID: 11557989]
[14]
Li, C.; Kim, H.J.; Back, S.K.; Na, H.S. Common and discrete mechanisms underlying chronic pain and itch: Peripheral and central sensitization. Pflugers Arch., 2021, 473(10), 1603-1615.
[http://dx.doi.org/10.1007/s00424-021-02599-y] [PMID: 34245379]
[15]
Rivera, L.; Gallar, J.; Pozo, M.A.; Belmonte, C. Responses of nerve fibres of the rat saphenous nerve neuroma to mechanical and chemical stimulation: An in vitro study. J. Physiol., 2000, 527(2), 305-313.
[http://dx.doi.org/10.1111/j.1469-7793.2000.t01-1-00305.x] [PMID: 10970431]
[16]
Liang, Y.F.; Haake, B.; Reeh, P.W. Sustained sensitization and recruitment of rat cutaneous nociceptors by bradykinin and a novel theory of its excitatory action. J. Physiol., 2001, 532(1), 229-239.
[http://dx.doi.org/10.1111/j.1469-7793.2001.0229g.x] [PMID: 11283237]
[17]
Herbert, M.K.; Just, H.; Schmidt, R.F. Histamine excites groups III and IV afferents from the cat knee joint depending on their resting activity. Neurosci. Lett., 2001, 305(2), 95-98.
[http://dx.doi.org/10.1016/S0304-3940(01)01817-1] [PMID: 11376892]
[18]
Koda, H.; Mizumura, K. Sensitization to mechanical stimulation by inflammatory mediators and by mild burn in canine visceral nociceptors in vitro. J. Neurophysiol., 2002, 87(4), 2043-2051.
[http://dx.doi.org/10.1152/jn.00593.2001] [PMID: 11929922]
[19]
Brusco, I.; Fialho, M.F.P.; Becker, G.; Brum, E.S.; Favarin, A.; Marquezin, L.P.; Serafini, P.T.; Oliveira, S.M. Kinins and their B1 and B2 receptors as potential therapeutic targets for pain relief. Life Sci., 2023, 314, 121302.
[http://dx.doi.org/10.1016/j.lfs.2022.121302] [PMID: 36535404]
[20]
Brunsden, A.M.; Grundy, D. Sensitization of visceral afferents to bradykinin in rat jejunum in vitro. J. Physiol., 1999, 521(2), 517-527.
[http://dx.doi.org/10.1111/j.1469-7793.1999.00517.x] [PMID: 10581320]
[21]
Koppert, W.; Martus, P.; Reeh, P.W. Interactions of histamine and bradykinin on polymodal C-fibres in isolated rat skin. Eur. J. Pain, 2001, 5(1), 97-106.
[http://dx.doi.org/10.1053/eujp.2001.0226] [PMID: 11394927]
[22]
Stebbins, C.L.; Stahl, G.L.; Theodossy, S.J.; Longhurst, J.C. Modulation of bradykinin-induced gastric-cardiovascular reflexes by histamine. Am. J. Physiol., 1992, 262(1 Pt. 2), R112-R119.
[PMID: 1733330]
[23]
Ashina, K.; Tsubosaka, Y.; Nakamura, T.; Omori, K.; Kobayashi, K.; Hori, M.; Ozaki, H.; Murata, T. Histamine induces vascular hyperpermeability by increasing blood flow and endothelial barrier disruption in vivo. PLoS One, 2015, 10(7), e0132367.
[http://dx.doi.org/10.1371/journal.pone.0132367] [PMID: 26158531]
[24]
Rex, D.A.B.; Deepak, K.; Vaid, N.; Dagamajalu, S.; Kandasamy, R.K.; Flo, T.H.; Keshava Prasad, T.S. A modular map of Bradykinin-mediated inflammatory signaling network. J. Cell Commun. Signal., 2022, 16(2), 301-310.
[http://dx.doi.org/10.1007/s12079-021-00652-0] [PMID: 34714516]
[25]
Gebhart, G.F., IV Visceral afferent contributions to the pathobiology of visceral pain. Am. J. Physiol. Gastrointest. Liver Physiol., 2000, 278(6), G834-G838.
[http://dx.doi.org/10.1152/ajpgi.2000.278.6.G834] [PMID: 10859211]
[26]
Fu, L.W.; Longhurst, J.C. Interactions between histamine and bradykinin in stimulation of ischaemically sensitive cardiac afferents in felines. J. Physiol., 2005, 565(3), 1007-1017.
[http://dx.doi.org/10.1113/jphysiol.2005.084004] [PMID: 15774520]
[27]
Katanosaka, K.; Banik, R.K.; Giron, R.; Higashi, T.; Tominaga, M.; Mizumura, K. Contribution of TRPV1 to the bradykinin-evoked nociceptive behavior and excitation of cutaneous sensory neurons. Neurosci. Res., 2008, 62(3), 168-175.
[http://dx.doi.org/10.1016/j.neures.2008.08.004] [PMID: 18789982]
[28]
Behrendt, M.; Solinski, H.J.; Schmelz, M.; Carr, R. Bradykinin-induced sensitization of Transient Receptor Potential Channel Melastin 3 calcium responses in mouse nociceptive neurons. Front. Cell. Neurosci., 2022, 16, 843225.
[http://dx.doi.org/10.3389/fncel.2022.843225] [PMID: 35496916]
[29]
Mazzone, S.B.; Canning, B.J. Synergistic interactions between airway afferent nerve subtypes mediating reflex bronchospasm in guinea pigs. Am. J. Physiol. Regul. Integr. Comp. Physiol., 2002, 283(1), R86-R98.
[http://dx.doi.org/10.1152/ajpregu.00007.2002] [PMID: 12069934]
[30]
Cesare, P.; McNaughton, P. A novel heat-activated current in nociceptive neurons and its sensitization by bradykinin. Proc. Natl. Acad. Sci. USA, 1996, 93(26), 15435-15439.
[http://dx.doi.org/10.1073/pnas.93.26.15435] [PMID: 8986829]
[31]
Revand, R.; Singh, S.K. Algogen-induced vasosensory reflexes modulate short-term heart rate variability parameters in experimental rat models. J. Basic Clin. Physiol. Pharmacol., 2022, 33(4), 429-437.
[http://dx.doi.org/10.1515/jbcpp-2020-0361] [PMID: 33873261]
[32]
Pethö, G.; Derow, A.; Reeh, P.W. Bradykinin-induced nociceptor sensitization to heat is mediated by cyclooxygenase products in isolated rat skin. Eur. J. Neurosci., 2001, 14(2), 210-218.
[http://dx.doi.org/10.1046/j.0953-816x.2001.01651.x] [PMID: 11553274]
[33]
Sugiura, T.; Tominaga, M.; Katsuya, H.; Mizumura, K. Bradykinin lowers the threshold temperature for heat activation of vanilloid receptor 1. J. Neurophysiol., 2002, 88(1), 544-548.
[http://dx.doi.org/10.1152/jn.2002.88.1.544] [PMID: 12091579]
[34]
Koda, H.; Minagawa, M.; Si-Hong, L.; Mizumura, K.; Kumazawa, T. H1-receptor-mediated excitation and facilitation of the heat response by histamine in canine visceral polymodal receptors studied in vitro. J. Neurophysiol., 1996, 76(3), 1396-1404.
[http://dx.doi.org/10.1152/jn.1996.76.3.1396] [PMID: 8890260]
[35]
Mizumura, K.; Minagawa, M.; Koda, H.; Kumazawa, T. Influence of histamine on the bradykinin response of canine testicular polymodal receptors in vitro. Inflamm. Res., 1995, 44(9), 376-378.
[http://dx.doi.org/10.1007/BF01797864] [PMID: 8846195]
[36]
Sandilands, E.A.; Crowe, J.; Cuthbert, H.; Jenkins, P.J.; Johnston, N.R.; Eddleston, M.; Bateman, D.N.; Webb, D.J. Histamine-induced vasodilatation in the human forearm vasculature. Br. J. Clin. Pharmacol., 2013, 76(5), 699-707.
[http://dx.doi.org/10.1111/bcp.12110] [PMID: 23488545]
[37]
Singh, S.K.; Deshpande, S.B. Buthus tamulus venom-induced vasosensory reflexes are mediated through efferent pathways in sympathetic and vagal parasympathetics. Neurosci. Lett., 2009, 464(3), 199-202.
[http://dx.doi.org/10.1016/j.neulet.2009.08.052] [PMID: 19703520]
[38]
Scholz, J.; Woolf, C.J. Can we conquer pain? Nat. Neurosci., 2002, 5(Suppl. 11), 1062-1067.
[http://dx.doi.org/10.1038/nn942] [PMID: 12403987]
[39]
Singh, S.K.; Deshpande, S.B. Intra-arterial injection of Mesobuthus tamulus venom elicits cardiorespiratory reflexes involving perivascular afferents. Toxicon, 2005, 46(7), 820-826.
[http://dx.doi.org/10.1016/j.toxicon.2005.08.014] [PMID: 16202438]
[40]
Singh, S.K.; Deshpande, S.B. Injection of Mesobuthus tamulus venom in distal segment of femoral artery evokes hyperventilatory and hypertensive responses in anaesthetised rats. Neurosci. Lett., 2008, 438(1), 64-66.
[http://dx.doi.org/10.1016/j.neulet.2008.04.037] [PMID: 18472330]
[41]
Singh, S.K.; Deshpande, S.B. Nociceptive vascular reflexes evoked by scorpion venom modulates cardiorespiratory parameters involving vanilloid receptor 1. Neurosci. Lett., 2009, 451, 194-198.
[http://dx.doi.org/10.1016/j.neulet.2009.01.012] [PMID: 19154775]
[42]
Revand, R.; Singh, S.K. Perivascular histamine receptors mediate vasosensory reflex responses elicited by thermal nociceptive stimuli in anaesthetised rat models. Indian J. Physiol. Pharmacol., 2021, 65, 146-152.
[http://dx.doi.org/10.25259/IJPP_258_2020]
[43]
Caterina, M.J.; Schumacher, M.A.; Tominaga, M.; Rosen, T.A.; Levine, J.D.; Julius, D. The capsaicin receptor: A heat-activated ion channel in the pain pathway. Nature, 1997, 389(6653), 816-824.
[http://dx.doi.org/10.1038/39807] [PMID: 9349813]
[44]
Latorre, R.; Brauchi, S.; Orta, G.; Zaelzer, C.; Vargas, G. ThermoTRP channels as modular proteins with allosteric gating. Cell Calcium, 2007, 42(4-5), 427-438.
[http://dx.doi.org/10.1016/j.ceca.2007.04.004] [PMID: 17499848]
[45]
Boillat, A.; Alijevic, O.; Kellenberger, S. Calcium entry via TRPV1 but not ASICs induces neuropeptide release from sensory neurons. Mol. Cell. Neurosci., 2014, 61, 13-22.
[http://dx.doi.org/10.1016/j.mcn.2014.04.007] [PMID: 24794232]
[46]
Jian, T.; Yang, N.; Yang, Y.; Zhu, C.; Yuan, X.; Yu, G.; Wang, C.; Wang, Z.; Shi, H.; Tang, M.; He, Q.; Lan, L.; Wu, G.; Tang, Z. TRPV1 and PLC participate in histamine H4 receptor-induced itch. Neural Plast., 2016, 2016, 1682972.
[http://dx.doi.org/10.1155/2016/1682972] [PMID: 26819760]

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