Advertisement

Sensory Nerves pp 185-225 | Cite as

Regulation of Cardiac Afferent Excitability in Ischemia

  • Liang-Wu Fu
  • John C. LonghurstEmail author
Chapter
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 194)

Abstract

The heart at the time of Sir William Harvey originally was thought to be an insensate organ. Today, however, we know that this organ is innervated by sensory nerves that course centrally though mixed nerve pathways that also contain parasympathetic or sympathetic motor nerves. Angina or cardiac pain is now well recognized as a pressure-like pain that occurs during myocardial ischemia when coronary artery blood flow is interrupted. Sympathetic (or spinal) afferent fibers that are either finely myelinated or unmyelinated are responsible for the transmission of information to the brain that ultimately allows the perception of angina as well as activation of the sympathetic nervous system, resulting in tachycardia, hypertension, and sometimes arrhythmias. Although early studies defined the importance of the vagal and sympathetic cardiac afferent systems in reflex autonomic control, until recently there has been little appreciation of the mechanisms of activation of the sensory endings. This review examines the role of a number of chemical mediators and their sources that are activated by the ischemic process. In this regard, patients with ischemic syndromes, particularly myocardial infarction and unstable angina, are known to have platelet activation, which leads to release of a number of chemical mediators, including serotonin, histamine, and thromboxane A2, all of which stimulate ischemically sensitive cardiac spinal afferent endings in the ventricles through specific receptor-mediated processes. Furthermore, protons from lactic acid, bradykinin, and reactive oxygen species, especially hydroxyl radicals, individually and frequently in combination, stimulate these endings during ischemia. Cyclooxygenase products appear to sensitize the endings to the action of bradykinin and histamine. These studies of the chemical mechanisms of activation of cardiac sympathetic afferent endings during ischemia have the potential to provide targeted therapies that can modify the angina and the deleterious reflex responses that have the potential to exacerbate ischemia and myocardial cell death.

Keywords

Sympathetic nervous system Cardiac spinal afferent Myocardial ischemia Ischemic mediator Nociceptor 

Notes

Acknowledgements

This work was supported, in part, by National Heart, Lung, and Blood Institute grant HL-66217. J.C.L holds the Larry K. Dodge Chair in Integrative Biology and the Susan Samueli Chair in Integrative Medicine.

References

  1. Abbott FV, Hong Y, Blier P (1996) Activation of 5-HT2A receptors potentiates pain produced by inflammatory mediators. Neuropharmacology 35:99–110PubMedGoogle Scholar
  2. Abe T, Morgan D, Sengupta JN, Gebhart GF, Gutterman DD (1998) Attenuation of ischemia-induced activation of cardiac sympathetic afferents following brief myocardial ischemia in cats. J Auton Nerv Syst 71:28–36PubMedGoogle Scholar
  3. Ahlgren SC, Levine JD (1994) Protein kinase C inhibitors decrease hyperalgesia and C-fiber hyperexcitability in the streptozotocin-diabetic rat. J Neurophysiol 72:684–692PubMedGoogle Scholar
  4. Aizawa H, Hirose T (1988) A possible mechanism of airway hyperresponsiveness induced by prostaglandin F2 alpha and thromooxane A2. Prosaglandins Leukot Essent Fatty Acids 33(3):185–189Google Scholar
  5. Anden NE, Olsson Y (1967) 5-hydroxytryptamine in normal and sectioned rat sciatic nerve. Acta Pathol Microbiol Scand 70:537–540PubMedGoogle Scholar
  6. Arita H, Nakano T, Hanasaki K (1989) Thromboxane A2: its generation and role in platelet activation. Prog Lipid Res 28:273–301PubMedGoogle Scholar
  7. Armstrong D, Dry RM, Keele CA, Markham JW (1951) Method for studying chemical excitants of cutaneous pain in man. J Physiol 115:59–60PubMedGoogle Scholar
  8. Ashton JH, Benedict CR, Fitzgerald C, Raheja S, Taylor A, Campbell WB, Buja LM, Willerson JT (1986) Serotonin as a mediator of cyclic flow variation in stenosed canine coronoary arteries. Circulation 73:572–578PubMedGoogle Scholar
  9. Baker D, Coleridge H, Coleridge J, Nerdrum T (1980) Search for a cardiac nociceptor: Stimulation by bradykinin of sympathetic afferent nerve endings in the heart of the cat. J Physiol 306:519–536PubMedGoogle Scholar
  10. Belville JS, Bennett WF, Lynch G (1979) A method for investigating the role of calcium in the shape change, aggregation and secretion of rat platelets. J Physiol 297:289–297PubMedGoogle Scholar
  11. Benedict CR, Mathew B, Rex KA, Cartwright J, Sordahl LA (1986) Correlation of plasma serotonin changes with platelet aggregation in an in vivo dog model of spontaneous occlusive coronary thrombus formation. Circ Res 58:58–67PubMedGoogle Scholar
  12. Berger HJ, Zaret BL, Speroff L, Cohen LS, Wolfson S (1977) Cardiac prostaglandin release during myocardial ischemia induced by atrial pacing in patients with coronary artery disease. Am J Cardiol 39:481–486PubMedGoogle Scholar
  13. Bevan S (1996) Intracellular messengers and signal transduction in nociceptors. In: Belmonte C, Cervero F (eds) Neurobiology of Nociceptors. Oxford University Press, Oxford, pp 298–324Google Scholar
  14. Bhoola KD, Figueroa CD, Worthy K (1992) Bioregulation of kinins: kallikreins, kininogens, and kininases. Pharmacol Rev 44:1–80PubMedGoogle Scholar
  15. Blackman SC, Dawson G, Antonakis K, Le Breton GC (1998) The identification and characterization of oligodendrocyte thromboxane A2 receptors. J Biol Chem 273:475–483PubMedGoogle Scholar
  16. Blunk J, Osiander G, Nischik M, Schmelz M (1999) Pain and inflammatory hyperalgesia induced by intradermal injections of human platelets and leukocytes. Eur J Pain 3:247–259PubMedGoogle Scholar
  17. Borg C, Lim CT, Yeomans DC, Dieter JP, Komiotis D, Anderson EG, Le Breton GC (1994) Purification of rat brain, rabbit aorta, and human platelet thromboxane A2/prostaglandin H2 receptors by immunoaffinity chromatography employing anti-peptide and anti-receptor antibodies. J Biol Chem 269:6109–6116PubMedGoogle Scholar
  18. Brunsden AM, Grundy D (1999) Sensitization of visceral afferents to bradykinin in rat jejunum in vitro. J Physiol 521 Pt 2:517–527Google Scholar
  19. Carrithers JA, Liu F, Shirer HW, Orr JA (1994) Mechanisms for techypneic response to the thromboxane A2 memetic U-46,619 in rabbits. Am J Physiol 266:R321–R327PubMedGoogle Scholar
  20. Coleman RA, Smith WL, Narumiya S (1994) VIII. International union of pharmacology classification of prostanoid receptors: properties, distribution, and structure of the receptors and their subtypes. Pharmacol Rev 46:205–229PubMedGoogle Scholar
  21. Coller BS (1997) Platelet GPIIb/IIIa antagonists: the first anti-integrin receptor therapeutics. J Clin Invest 100:S57–S60PubMedGoogle Scholar
  22. Couture R, Harrisson M, Vianna RM, Cloutier F (2001) Kinin receptors in pain and inflammation. Eur J Pharmacol 429:167–176Google Scholar
  23. Cox DA, Vita JA, Treasure CB, Fish RD, Seiwyn AP, Ganz P (1989) Reflex increase in blood pressure during intra-coronary administration of adenosine in man. J Clin Invest 84:592–596PubMedGoogle Scholar
  24. Crea F, Pupita G, Galassi A, El-Tamimi H, Kaski JC, Davis G, Maseri A (1990) Role of adenosine in pathogenesis of angina pain. Circulation 81:164–182PubMedGoogle Scholar
  25. Crea F, Gaspardone A, Kaski JC, Davis G, Maseri A (1992) Relation between stimulation site of cardiac afferent nerves by adenosine and distribution of cardiac pain: results of a study in patients with stable angina. JACC 20:1498–1502PubMedGoogle Scholar
  26. Delyani JA, Van Wylen GL (1994) Endocardial and epicardial interstitial purines and lactate during graded ischemia. Am J Physiol 226:H1019–H1026Google Scholar
  27. Dibner-Dunlap ME, Kinugawa T, Thames MD (1993) Activation of cardiac sympathetic afferents: effects of exogenous adenosine and adenosine analogues. Am J Physiol 265:H395–H400PubMedGoogle Scholar
  28. Dray A (1995) Inflammatory mediators of pain. Br J Anaesth 75:125–131PubMedGoogle Scholar
  29. Evans RG, Ludbrook J, Michalicek J (1990) Characteristis of cardiovascular reflexes originating from 5-HT3 receptors in the heart and lungs of unanaethetized rabbits. Clin Exp Pharmacol Physiol 17:665–679PubMedGoogle Scholar
  30. Ferrari R (1994) Oxygen-free radicals at myocardial level: effects of ischaemia and reperfusion. Adv Exp Med Biol 366:99–111PubMedGoogle Scholar
  31. Ferreira SH (1972) Prostaglandins, aspirin-like drugs and analgesia. Nat New Biol 240:200–203PubMedGoogle Scholar
  32. Fitzgerald DJ (1991) Platelet activation in the pathogenesis of unstable angina: importance in determining the response to plasminogen activators. Am J Cardiol 68:51B–57BPubMedGoogle Scholar
  33. Fitzgerald DJ, Roy L, Catella F, Fitzgerald GA (1986) Platelet activation in unstable coronary disease. N Engl J Med 315:983–989PubMedGoogle Scholar
  34. Flores NA, Sheridan DJ (1994) The pathophysiological role of platelets during myocardial ischemia. Cardiovasc Res 28:295–302PubMedGoogle Scholar
  35. Flores NA, Goulielmos NV, Seghatchian MJ, Sheridan DJ (1994) Myocardial ischemia induces platelet activation with adverse electrophysiological and arrhythmogenic effects. Cardiovasc Res 28:1662–1671PubMedGoogle Scholar
  36. Folts JD (1994) Platelet aggregation in partially obstructed vessels and its elimination with aspirin. Circulation 54:365–370Google Scholar
  37. Folts JD, Crowell EB Jr, Rowe GG (1976) Platelet aggregation in partially obstructed vessels and its elimination with aspirin. Circulation 54:365–370PubMedGoogle Scholar
  38. Frangogiannis N, ML Lindsey, LH Michael, KA Youker, RB Bressler, LH Mendoza, RN Spengler, CW Smith, ML Entman (1998) Resident cardiac mast cells degranulate and release preformed TNF-α, initiating the cytokine cascade in experimental canaine myocardial ischemia/reperfusion. Circulation 98:699–710PubMedGoogle Scholar
  39. Fu L-W, Longhurst JC (1998) Role of 5-HT3 receptors in activation of abdominal sympathetic C-fibre afferents during ischemia in cats. J Physiol (Lond) 509:729–740Google Scholar
  40. Fu L-W, Longhurst JC (2002a) Activated platelets contribute to stimulation of cardiac afferents during ischaemia in cats: role of 5-HT3 receptors. J Physiol (Lond) 544:897–912Google Scholar
  41. Fu L-W, Longhurst JC (2002b) Role of activated platelets in excitation of cardiac afferents during myocardial ischemia in cats. Am J Physiol 282:H100–H109Google Scholar
  42. Fu L-W, Longhurst JC (2005) Interactions between histamine and bradykinin in stimulation of ischaemically sensitive cardiac afferents in felines. J Physiol (Lond) 565:1007–1017Google Scholar
  43. Fu L-W, Longhurst JC (2008) Reciprocal interactions between bradykinin and thromboxane A2 during stimulation of ischemically sensitive cardiac spinal afferents. FASEB J 22:1230.4Google Scholar
  44. Fu L-W, Pan H-L, Longhurst JC (1997) Endogenous histamine stimulates ischemically sensitive abdominal visceral afferents through H1 receptors. Am J Physiol 273:H2726–H2737PubMedGoogle Scholar
  45. Fu L-W, Phan A, Longhurst JC (2008a) Myocardial Ischemia-Mediated Excitatory Reflexes: A New Function for Thromboxane A2? Am J Physiol 295:H2530–H2540Google Scholar
  46. Fu L-W, Schunack W, Longhurst JC (2005) Histamine contributes to ischemia-related activation of cardiac spinal afferents: role of H1 receptors and PKC. J Neurophysiol 93:713–722PubMedGoogle Scholar
  47. Fu LW, Guo ZL, Longhurst JC (2008b) Undiscovered role of endogenous TxA2 in activation of cardiac sympathetic afferents during ischemia. J Physiol 586(13):3287–3300PubMedGoogle Scholar
  48. Fujimori T, Yamanishi Y, Yamatsu K, Tajima T (1982) High performance liquid chromatography (HPLC) determination of endogenous serotonin released from aggregating platelets. J Pharmacol Methods 7:105–113PubMedGoogle Scholar
  49. Furci L, Fitzgerald DJ, Fitzgerald GA (1991) Heterogeneity of prostaglandin H2/thromboxane A2 receptors: distinct subtypes mediate vascular smooth muscle contraction and platelet aggregation. J Pharmacol Exp Ther 258:74–81PubMedGoogle Scholar
  50. Gao H, Welch WJ, DiBona GF, Wilcox CS (1997) Sympathetic nervous system and hypertension during prolonged TxA2/PGH2 receptor activation in rats. Am J Physiol 273:H734–H739PubMedGoogle Scholar
  51. Gebhart GF (2000) Pathobiology of visceral pain: molecular mechanisms and therapeutic implications IV. Visceral afferent contributions to the pathobiology of visceral pain. Am J Physiol Gastrointest Liver Physiol 278:G834–G838PubMedGoogle Scholar
  52. Ginsburg R, Bristow M, Kantrowitz N, Baim D, Harrison D (1981) Histamine provocation of clinical coronary artery spasm: Implications concerning pathogenesis of variant angina pectoris. Am Heart J 102:819–822PubMedGoogle Scholar
  53. Gnecchi-Ruscone T, Montano N, Contini M, Guazzi M, Lombardi F, Malliani A (1995) Adenosine activates cardiac sympathetic afferent fibers and potentiates the excitation induced by coronary occlusion. J Auton Nerv Syst 53:175–184PubMedGoogle Scholar
  54. Golino P, Piscione F, Benedict C, Anderson H, Cappelli-Bigazzi M, Indolfi C, Condorelli M, Chiariello M, Willerson J (1994) Local effect of serotonin released during coronary angioplasty. N Engl J Med 330:523–528PubMedGoogle Scholar
  55. Grande P, Grauholt A-M, Madsen JK (1990) Unstable angina pectoris: platelet behavior and prognosis in progressive angina and intermediate coronary syndrome. Circulation 81(suppl I):I16–I19PubMedGoogle Scholar
  56. Grill HP, Zweier P, Kuppusamy ML, Weisfeldt ML, Flaherty JT (1992) Direct measurement of myocardial free radical generation in an in vivo model: effects of postischemic reperfusion and treatment with human recombinant superoxide dismutase. J Am Coll Cardiol 20:1604–1611PubMedGoogle Scholar
  57. Grisham MB, Granger DN (1988) Neutrophil-mediated mucosal injury: role of reactive oxygen metabolites. Dig Dis Sci 33:6S–15SPubMedGoogle Scholar
  58. Grundy D, Blackshae LA, Hillsley K (1994) Role of 5-hydroxytryptamine in gastrointestinal chemosensitivity. Dig Dis Sci 30(suppl):44S–47SGoogle Scholar
  59. Guo Z-L, Longhurst J (2000) Role of cAMP in activation of ischemically sensitive abdominal visceral afferents. Am J Physiol 278:H843–H852Google Scholar
  60. Guo Z-L, Fu L-W, Symons J, Longhurst J (1998) Signal transduction in activation of ischemically sensitive abdominal visceral afferents: role of PKC. Am J Physiol 275:H1024–H1031PubMedGoogle Scholar
  61. Guo Z-L, JD Symons, JC Longhurst (1999) Activation of visceral afferents by bradykinin and ischemia: independent roles of PKC and prostaglandins. Am J Physiol 276:H1884–H1891PubMedGoogle Scholar
  62. Halliwell B (1989) Protection against tissue damage in vivo by desferrioxamine: what is its mechanism of action? Free Radic Biol Med 7:645–651PubMedGoogle Scholar
  63. Halliwell B, Gutteridge JMC (1990) Role of free radicals and catalytic metal ions in human disease. An overview. Meth Enzymol 186:1–85Google Scholar
  64. Hashimoto K, Hirose M, Furukawa S, Hayakawa H, Kimura E (1977) Changes in hemodynamics and bradykinin concentration in coronary sinus blood in experimental coronary artery occlusion. Jpn Heart J 5:679–689Google Scholar
  65. Hendrickson SC, St Louis JD, Lowe JE, bdel-Aleem S (1997) Free fatty acid metabolism during myocardial ischemia and reperfusion. Mol Cell Biochem 166:85–94PubMedGoogle Scholar
  66. Herbert MK, Just H, Schmidt RF (2001) Histamine excites groups III and IV afferents from the cat knee joint depending on their resting activity. Neurosci Lett 305:95–98PubMedGoogle Scholar
  67. Hill SJ, Ganellin CR, Timmerman H, Schwartz JC, Shankley NP, Young JM, Schunack W, Levi R, Haas HL (1997) International union of pharmacology. XIII. Classification of histamine receptors. Pharmacol Rev 49:253–278PubMedGoogle Scholar
  68. Hiramatsu Y, Gikakis N, Anderson III HL, Gorman III JH, Marcinkiewicz C, Gould RJ, Niewiarowski S, Edmunds LH Jr (1997) Tirofiban provides “platelet anesthesia” during cardiopulmonary bypass in baboons. J Thorac Cardiovasc Surg 113:193Google Scholar
  69. Hirsh P, Hillis L, Campbell W, Firth B, Willerson J (1981) Release of prostaglandins and thromboxane into the coronary circulation in patients with ischemic heart disease. N Engl J Med 304:685–691PubMedGoogle Scholar
  70. Holmsen H (1985) Platelet metabolism and activation. Sem Hematol 22:219–240Google Scholar
  71. Holzer P (2001) Gastroduodenal mucosal defense: coordination by a network of messengers and mediators. Curr Opin Gastroenterol 17:489–496PubMedGoogle Scholar
  72. Hong JL, Kwong K, Lee LY (1997) Stimulation of pulmonary C fibers by lactic acid in rats: concentrations of H+ and lactate ions. J Physiol 500:319–329PubMedGoogle Scholar
  73. Hoyer D, Clarke DE, Fozard JR, Hartig PR, Martin GR, Mylecharane EJ (1994) International union of parmacology classification of receptors for 5-hydroxytryptamine (serotonin). Pharmacol Rev 46:157–203PubMedGoogle Scholar
  74. Hsu KS, Han WM (1996) Thromboxane A2 agonist modulation of excitatory synaptic transmission in hte rat hippocampal slice. Br J Pharmacol 118:2220–2227PubMedGoogle Scholar
  75. Huang H-S, Pan H-L, Stahl G, Longhurst J (1995a) Ischemia- and reperfusion-sensitive cardiac sympathetic afferents: influence of H2O2 and hydroxyl radicals. Am J Physiol 269:H888–H901PubMedGoogle Scholar
  76. Huang H-S, Stahl G, Longhurst J (1995b) Cardiac-cardiovascular reflexes induced by hydrogen peroxide in cats. Am J Physiol 268:H2114–H2124PubMedGoogle Scholar
  77. Huang MH, Sylven C, Horackova M, Armour JA (1995c) Ventricular sensory neurons in canine dorsal root ganglia: effects of adenosine and substance P. Am J Physiol 269:R318–R324PubMedGoogle Scholar
  78. Ichinose M, Barnes PJ (1990) Histamine H3 receptors modulate antigen-induced bronchoconstriction in guinea pigs. J Allergy Clin Immunol 86:491–495PubMedGoogle Scholar
  79. Imamura M, Seyedi N, Lander HM, Levi R (1995) Functional idendification of histamine H3-receptors in the human heart. Circ Res 77:206–210PubMedGoogle Scholar
  80. Imamura M, Smith NC, Garbarg M, Levi R (1996) Histamine H3-receptor-mediated inhibition of calcitonin gene-related peptide release from cardiac C fibers. A regulatory negative-feedback loop. Circ Res 78:863–869PubMedGoogle Scholar
  81. Immke DC, McCleskey EW (2003) Protons open acid-sensing ion channels by catalyzing relief of Ca2+ blockade. Neuron 37:75–84PubMedGoogle Scholar
  82. Jackson JH, White CW, Parker NB, Ryan JW, Repine JE (1985) Dimethylthiourea consumption reflects H2O2 concentrations and severity of acute lung injury. J Appl Physiol 59:1995–1998PubMedGoogle Scholar
  83. Jennings RB, Reimer KA, Hill ML, Mayer SE (1981) Total ischemia in dog heart in vitro. 1. Comparison of high energy phosphate production, utilization, an depletion, and of adenine nucleotide catabolism in total ischemia in vitro vs. severe ischemia in vivo. Circulation 49:892–900Google Scholar
  84. Jordan D (2005) Vagal control of the heart: central serotonergic (5-HT) mechanisms. Exp Physiol 90:175–181PubMedGoogle Scholar
  85. Jordt SE, Tominaga M, Julius D (2000) Acid potentiation of the capsaicin receptor determined by a key extracellular site. Proc Natl Acad Sci USA 97:8134–8139PubMedGoogle Scholar
  86. Kappagoda CT, Linden RJ, Mary DASG (1977) Atrial receptors in the dog and rabbit. J Physiol 272:799–815PubMedGoogle Scholar
  87. Kappagoda CT, Linden RJ, Sivananthan N (1979) The nature of the atrial receptors responsible for a reflex increase in heart rate in the dog. J Physiol 291:393–412PubMedGoogle Scholar
  88. Karla W, Shams H, Orr JA, Scheid P (1992) Effects of the thromboxane A2 mimetic, U46,619, on pulmonary vagal afferents in the cat. Respir Physiol 87:383–396PubMedGoogle Scholar
  89. Kashiba H, Fukui H, Morikawa Y, Senba E (1999) Gene expression of histamine H1 receptor in guinea pig primary sensory neurons: a relationship between H1 receptor mRNA-expressing neurons and peptidergic neurons. Brain Res Mol Brain Res 66:24–34PubMedGoogle Scholar
  90. Kaufman MP, Baker DG, Coleridge HM, Coleridge JCG (1980) Stimulation by bradykinin of afferent vagal C-fibers with chemosensitive endings in the heart and aorta of the dog. Circ Res 46:476–484PubMedGoogle Scholar
  91. Kaufman MP, Iwamoto GA, Longhurst JC, Mitchell JH (1982) Effects of capsaicin and bradykinin on afferent fibers with endings in skeletal muscle. Circ Res 50:133–139PubMedGoogle Scholar
  92. Kenagy J, VanCleave J, Pazdernik L, Orr JA (1997) Stimulation of group III and IV afferent nerves from the hindlimb by thromboxane A2. Brain Res 744:175–178PubMedGoogle Scholar
  93. Kimura E, Hashimoto K, Furukawa S, Hayakawa H (1973) Changes in bradykinin level in coronary sinus blood after the experimental occulsion of a coronary artery. Am Heart J 85:635–647PubMedGoogle Scholar
  94. Koda H, Mizumura K (2002) Sensitization to mechanical stimulation by inflammatory mediators and by mild burn in canine visceral nociceptors in vitro. J Neurophysiol 87:2043–2051PubMedGoogle Scholar
  95. Koda H, Minagawa M, Si-Hong L, Mizumura K, Kumazawa T (1996) H1-receptor-mediated excitation and facilitation of the heat response by histamine in canine visceral polymodal receptors studied in vitro. J Neurophysiol 76:1396–1404PubMedGoogle Scholar
  96. Koppert W, Martus P, Reeh PW (2001) Interactions of histamine and bradykinin on polymodal C-fibres in isolated rat skin. Eur J Pain 5:97–106PubMedGoogle Scholar
  97. Kounis NG, Zavras GM (1991) Histamine-induced coronary artery spasm: the concept of allergic angina. Br J Clin Pract 45:121–127PubMedGoogle Scholar
  98. Kuppusamy P, Zweier JL (1989) Characterization of free radical generation by xanthine oxidase. Evidence for hydroxyl radical generation. J Biol Chem 264:9880–9884PubMedGoogle Scholar
  99. Laine P, Kaartinen M, Penttila A, Panula P, Paavonen T, Kovanen PT (1999) Association between myocardial infarction and the mast cells in the adventitia of the infarct-related coronary artery. Circulation 99:361–369PubMedGoogle Scholar
  100. Laine P, Naukkarinen A, Heikkila L, Penttila A, Kovanen PT (2000) Adventitial mast cells connect with sensory nerve fibers in atherosclerotic coronary arteries. Circulation 101:1665–1669PubMedGoogle Scholar
  101. Leanos OL, Hong E, Amezcua JL (1995) Reflex circulatory collapse following intrapulmonary entrapment of activated platelets: mediation via 5-HT3 receptor stimulation. Br J Pharmacol 116:2048–2052PubMedGoogle Scholar
  102. Lefkovits J, Plow EF, Topol EJ (1995) Platelet glycoprotein IIb/IIIa receptors in cardiovascular medicine. N Engl J Med 332:1553–1559PubMedGoogle Scholar
  103. Lehtosalo JI, Uusitalo H, Laakso J, Palkama A, Harkonen M (1984) Biochemical and immunohistochemical determination of 5-hydroxytryptamine located in mast cells in the trigeminal ganglion of the rat and guinea pig. Histochemistry 80:219–223PubMedGoogle Scholar
  104. Lew WYW, Longhurst JC (1986) Substance P, 5-hydroxytryptamine, and bradykinin stimulate abdominal visceral afferents. Am J Physiol 250:R465–R473PubMedGoogle Scholar
  105. Lewy RI, Wiener L, Walinsky P, Lefer AM, Silver MJ, Smith JB (1980) Thromboxane release during pacing-induced angina pectoris: possible vasoconstrictor influence on the coronary vasculature. Circulation 61:1165–1171PubMedGoogle Scholar
  106. Lincoff MA, Califf RM, Topol EJ (2000) Platelet glycoprotein IIb/IIia receptor blockade in coronary artery disease. J A Coll Cardiol 35:1103–1115Google Scholar
  107. Longhurst JC (1984) Cardiac receptors: Their function in health and disease. Prog Cardiovasc Dis XXVII:201–222Google Scholar
  108. Longhurst J, Dittman L (1987) Hypoxia, bradykinin, and prostaglandins stimulate ischemically sensitive visceral afferents. Am J Physiol 253:H556–H567PubMedGoogle Scholar
  109. Longhurst J, Rotto D, Kaufman M, Stahl G (1991) Ischemically sensitive abdominal visceral afferents: response to cyclooxygenase blockade. Am J Physiol 261:H2075–H2081PubMedGoogle Scholar
  110. Longhurst J, Tjen-A-Looi S, Fu L-W (2001) Cardiac sympathetic afferent activation provoked by myocardial ischemia and reperfusion: mechanisms and reflexes. Ann N Y Acad Sci 940:74–95PubMedGoogle Scholar
  111. Malliani A, Lombardi F, Pagani M (1981) Functions of afferents in cardiovascular sympathetic nerves. J Auton Nerv Syst 3:231–236PubMedGoogle Scholar
  112. Mark AL, Abboud FM, Heistad DD, Schmid PG, Johannsen UJ (1974) Evidence against the presence of ventricular chemoreceptors activated by hypoxia and hypercapnia. Am J Physiol 227:273–279Google Scholar
  113. Masini E, Giannella E, Bianchi S, Mannaioni PF (1987) Histamine and lactate dehydrogenase (LDH) release in ischemic myocardium of the guinea-pig. Agents Actions 20:281–283PubMedGoogle Scholar
  114. Masini E, Di Bello MG, Raspanti S, Fomusi Ndisang J, Baronti R, Cappugi P, Mannaioni PF (1998) The role of histamine in platelet aggregation by physiological and immunological stimuli. Inflamm Res 47:211–220PubMedGoogle Scholar
  115. Mazzone SB, Canning BJ (2002) Synergistic interactions between airway afferent nerve subtypes mediating reflex bronchospasm in guinea pigs. Am J Physiol Regul Integr Comp Physiol 283:R86–R98PubMedGoogle Scholar
  116. Mehta J, Mehta P, Feldman R, Horalek C (1984) Thromboxane release in coronary artery disease: spontaneous versus pacing-induced angina. Am Heart J 107:286–292PubMedGoogle Scholar
  117. Meller ST, Gebhart GF (1992) A critical review of the afferent pathways and the potential chemical mediators involved in cardiac pain. Neuroscience 48:501–524PubMedGoogle Scholar
  118. Meyers KM, Holsmen H, Seachord CL (1982) Comparative study of platelet dense granule constituents. Am J Physiol 243:R454–R461PubMedGoogle Scholar
  119. Middlekauff HR, Chiu J (2004) Cyclooxygenase products sensitize muscle mechanoreceptors in healthy humans. Am J Physiol Heart Circ Physiol 5:H1944–H1949Google Scholar
  120. Mizumura K, Minagawa M, Koda H, Kumazawa T (1995) Influence of histamine on the bradykinin response of canine testicular polymodal receptors in vitro. Inflamm Res 44:376–378PubMedGoogle Scholar
  121. Muja N, Blackman SC, Le Breton GC, DeVries GH (2001) Identification and functional characterization of thromboxane A2 receptors in Schwann cells. J Neurochem 78:446–456PubMedGoogle Scholar
  122. Nakahodo K, Saitoh S, Nakamura M, Kosugi T (1994) Histamine release from rabbit platelets by platelet-activating factor (PAF). Arerugi 43:501–510PubMedGoogle Scholar
  123. Nandam LS, Jhaveri D, Bartlett P (2007) 5-HT7, neurogenesis and antidepressants: a promising therapeutic axis for treating depression. Clin Exp Pharmacol Physiol 34:546–551PubMedGoogle Scholar
  124. Nerdrum T, Baker D, Coleridge H, Coleridge J (1986) Interaction of bradykinin and prostaglandin E1 on cardiac pressor reflex and sympathetic afferents. Am J Physiol 250:R815–R822PubMedGoogle Scholar
  125. Nicolson TA, Bevan S, Richards CD (2002) Characterisation of the calcium responses to histamine in capsaicin-sensitive and capsaicin-insensitive sensory neurones. Neuroscience 110:329–338PubMedGoogle Scholar
  126. Ninkovic M, Hunt SP (1985) Opiate and histamine H1 receptors are present on some substance P-containing dorsal root ganglion cells. Neurosci Lett 53:133–137PubMedGoogle Scholar
  127. Nishi K, Sakanashi M, Takenaka F (1977) Activation of afferent cardiac sympathetic nerve fibers of the cat by pain producing substances and by noxious heat. Pflugers Arch 372:53–61PubMedGoogle Scholar
  128. O'Neill CA, Fu L-W, Halliwell B, Longhurst JC (1996) Hydroxyl radical production during myocardial ischemia and reperfusion in cats. Am J Physiol 271:H660–H667PubMedGoogle Scholar
  129. Oberg B, Thoren PN (1973) Circulatory responses to stimulation of medullated and non-medullated afferents in the cardiac nerve in the cat. Acta Physiol Scand 87:121–132PubMedGoogle Scholar
  130. Opie LH, Owen P, Thomas M, Samson R (1973) Coronary sinus lactic measurements in assessment of myocardial ischemia. Am J Cardiol 32:295–305PubMedGoogle Scholar
  131. oude Egbrink MG, Tangelder GJ, Slaaf DW, Reneman RS (1993) Different roles of prostaglandins in thromboembolic processes in arterioles and venules in vivo. Thromb Haemost 70:826–833PubMedGoogle Scholar
  132. Packham MA, Guccione MA, Greenberg JP, Kinlough-Rathbone RL, Mustard JF (1977) Release of 14C-serotonin during initial platelet changes induced by thrombin, collagen, or A23187. Blood 50:915–926PubMedGoogle Scholar
  133. Packham MA, Rand ML, Ruben DH, Kinlough-Rathbone RL (1991) Effect of calcium concentration and inhibitors on the responses of platelets stimulated with collagen: contrast between human and rabbit platelets. Comp Biochem Physiol A 99:551–557PubMedGoogle Scholar
  134. Pagani M, Pizzinelli R, furlan R, Guzzetti S, Rimoldi O, Sandrone G, Malliani A (1985) Analysis of the pressor sympathetic reflex produced by intracoronary injections of bradykinin in conscious dogs. Circ Res 56:175–183PubMedGoogle Scholar
  135. Paintal AS (1973) Vagal sensory receptors and their reflex effects. Physiol Rev 53:159–227PubMedGoogle Scholar
  136. Pal P, Koley J, Bhattacharyya S, Gupta JS, Koley B (1989) Cardiac nociceptors and ischemia: role of sympathetic afferents in cat. Jpn J Physiol 39:131–144PubMedGoogle Scholar
  137. Pan H-L, Longhurst J (1995) Lack of a role of adenosine in activation of ischemically sensitive cardiac sympathetic afferents in cats. Am J Physiol 269:H106–H113PubMedGoogle Scholar
  138. Pan H-L, Stahl GL, Rendig SV, Carretero OA, Longhurst JC (1994) Endogenous BK stimulates ischemically sensitive abdominal visceral C fiber afferents through kinin B2 receptors. Am J Physiol 267:H2398–H2406PubMedGoogle Scholar
  139. Pan H-L, Longhurst JC, Eisenach JC, Chen S-R (1999) Role of protons in activation of cardiac sympathetic C-fiber afferents during ischemia. J Physiol 518.3:857–866Google Scholar
  140. Parratt JR, Cokerm S (1981) The significance of prostaglandin and thromboxane release in acute myocardial ischemia. In: Forster W (ed) Rostaglandins and Thromboxanes: Proceedings of the Third International Symposium on Prostaglandins and Thromboxanes in the Cardiovascular System. Pergamon, New York, pp 21–25Google Scholar
  141. Patterson L, Patterson L, Patterso, Patterson LM, Zheng H, Ward SM, Berhoud H-R (2003) Vanilloid receptor (VR1) expression in vagal afferent neurons innervating the gastrointestinal tract. Cell Tissue Res 311:277–287PubMedGoogle Scholar
  142. Peroutka SJ (1994) 5-Hydroxytryptamine receptors. J Neurochem 60:408–416Google Scholar
  143. Petho G, Derow A, Reeh PW (2001) Bradykinin-induced nociceptor sensitization to heat is mediated by cyclooxygenase products in isolated rat skin. Eur J Neurosci 14:210–218PubMedGoogle Scholar
  144. Phillips DR, Scarborough RM (1997) Clinical pharmacology of eptifibatide. Am J Cardiol 80:11B–20BPubMedGoogle Scholar
  145. Pickar JG (1998) The thromboxane A2 mimetic U-46619 inhibits somatomotor activity via a vagal reflex from the lung. Am J Physiol 275:R706–R712PubMedGoogle Scholar
  146. Poole-Wilson PA (1978) Measurement of myocardial intracellular pH in pathological states. J Mol Cell Cardiol 10:511–526PubMedGoogle Scholar
  147. Rang HP, Bevan SJ, Dray A (1991) Chemical activation of nociceptive peripheral neurons. Br Med Bull 47:534–548PubMedGoogle Scholar
  148. Rao GHR (1993) Physiology of blood platelet activation. Indian J Physiol Pharmacol 37:263–275PubMedGoogle Scholar
  149. Repka-Ramirez MS (2003) New concepts of histamine receptors and actions. Curr Allergy Asthma Rep 3:227–231PubMedGoogle Scholar
  150. Rhodes KF, Coleman J, Lattimer N (1992) A component of 5-HT-evoked depolarization of the rat isolated vagus nerve is mediated by a putative 5-HT4 receptor. Naunyn Schemiedebergs Arch Pharmacol 346:496–503Google Scholar
  151. Richardson BP (1990) Serotonin and nociception. Ann N Y Acad Sci 600:511–519PubMedGoogle Scholar
  152. Ringkamp M, Schmelz M, Kress M, Allwang M, Ogilvie A, Reeh PW (1994) Activated human platelets in plasma excite nociceptors in rat skin, in vitro. Neurosci Lett 170:103–106PubMedGoogle Scholar
  153. Rotto DM, Stebbins CL, Kaufman MP (1989) Reflex cardiovascular and ventilatory responses to increasing H+ activity in cat hindlimb muscle. J Appl Physiol 67:256–263PubMedGoogle Scholar
  154. Rotto D, Schultz H, Longhurst J, Kaufman M (1990) Sensitization of group III muscle afferents to static contraction by arachidonic acid metabolism. J Appl Physiol 68:861–867PubMedGoogle Scholar
  155. Rupniak HT, Joy KA, Atkin C (2000) Oxidative neuropathology and putative chemical entities for Alzheimer's disease: neuroprotective effects of salen-manganese catalytic anti-oxidants. Neurotox Res 2:167–178PubMedGoogle Scholar
  156. Sakata K, Yoshida H, Hoshino T, Kurata C (1996) Sympathetic nerve activity in the spasm-induced coronary artery region is associated with disease activity of vasospastic angina. J Am Coll Cardiol 28:460–464PubMedGoogle Scholar
  157. Saxena SP, Brandes LJ, Becker AB, Simons KJ, LaBella FS, Gerrard JM (1989) Histamine is an intracellular messenger mediating platelet aggregation. Science 243:1596–1599PubMedGoogle Scholar
  158. Schaefer S, RA Valente, LJ Laslett, JC Longhurst (1996) Cardiac reflex effects of intracoronary bradykinin in humans. J Investig Med 492:841–850Google Scholar
  159. Schmelz M, Osiander G, Blunk J, Ringkamp M, Reeh PW, Handwerker HO (1997) Intracutaneous injections of platelets cause acute pain and protracted hyperalgesia. Neurosci Lett 226:171–174PubMedGoogle Scholar
  160. Shams H, Scheid P (1990) Effects of thromboxane on respiration and pulmonary circulation in the cat: role of vagus nerve. J Appl Physiol 68:2042–2046PubMedGoogle Scholar
  161. Sommer C (2004) Serotonin in pain and analgesia: actions in the periphery. Mol Neurobiol 30:117–125PubMedGoogle Scholar
  162. Stahl G, Longhurst J (1992) Ischemically sensitive visceral afferents: importance of H+ derived from lactic acid and hypercapnia. Am J Physiol 262:H748–H753PubMedGoogle Scholar
  163. Stahl G, Pan H-L, Longhurst J (1993) Activation of ischemia and reperfusion-sensitive abdominal visceral C fiber afferents: role of hydrogen peroxide and hydroxyl radicals. Circ Res 72:1266–1275PubMedGoogle Scholar
  164. Stary HC (1990) The sequence of cell and matrix changes in atherosclerotic lesions of coronary arteries in the first forty years of life. Eur Heart J 11(suppl E):3–19PubMedGoogle Scholar
  165. Staszewka-Barczak J, Ferreira SH, Vane JR (1976) An excitatory nociceptive cardiac reflex elicited by bradykinin and potentiated by prostaglandins and myocardial ischaemia. Cardiovasc Res 10:314–327PubMedGoogle Scholar
  166. Staszewska-Woolley J, Woolley G (1989) Participation of the kallikrein-kinin-receptor system in reflexes arising from neural afferents in the dog epicardium. J Physiol (Lond) 419:33–44Google Scholar
  167. Stebbins CL, Longhurst JC (1985) Bradykinin-induced chemoreflexes from skeletal muscle: implications for the exercise reflex. J Appl Physiol 59:56–63PubMedGoogle Scholar
  168. Stebbins CL, Longhurst JC (1986) Bradykinin in the reflex cardiovascular responses to static muscular contraction. J Appl Physiol 61:271–279PubMedGoogle Scholar
  169. Stebbins CL, Theodossy SJ, Longhurst JC (1991) Cardiovascular reflexes evoked by histamine stimulation of the stomach. Am J Physiol 261:H1098–H1105Google Scholar
  170. Stebbins C, Stahl G, Theodossy S, Longhurst J (1992) Modulation of bradykinin-induced gastric-cardiovascular reflexes by histamine. Am J Physiol 262:R112–R119PubMedGoogle Scholar
  171. Steen KH, Steen AE, Reeh PW (1995) A dominant role of acid pH in inflammatory excitation and sensitization of nociceptors in rat skin, in vivo. J Neurosci 15:3982–3989PubMedGoogle Scholar
  172. Stegmeier K, Pill J, Muller-Beckmann B, Schmidt FH, Witte EC, Wolff HP, Patscheke H (1984) The pharmacological profile of the thromboxane A2 antagonist BM 13.177. A new anti-platelet and anti-thrombotic drug. Thromb Res 35:379–395PubMedGoogle Scholar
  173. Stormorken H (1986) Platelets in hemostasis and thrombosis. In: Holmsen H (ed) Platelet responses and metabolism, vol 1. CRC, Boca Raton, pp 3–32Google Scholar
  174. Sun SY, Wang W, Schultz HD (2001) Activation of cardiac afferents by arachidonic acid: relative contributions of metabolic pathways. Am J Physiol Heart Circ Physiol 281:H93–H104PubMedGoogle Scholar
  175. Sylven C, Beemann B, Jonzon B, Brandt R (1986) Angina pectoris-like pain provoked by intravenous adenosine. Br Med J 293:227–230Google Scholar
  176. Taiwo YO, Levine JD (1991) Further confirmation of the role of adenyl cyclase and of cAMP-dependent protein kinase in primary afferent hyperalgesia. Neuroscience 44:131–135PubMedGoogle Scholar
  177. Taiwo YO, Levine JD (1992) Serotonin is a directly-acting hyperalgesic agent in the rat. Neuroscience 48:485–490PubMedGoogle Scholar
  178. Taiwo Y, Goetzl EJ, Levine JD (1987) Hyperalgesia onset latency suggests a hierarchy of action. Brain Res 423:333–337PubMedGoogle Scholar
  179. Thoren P (1973) Evidence for a depressor reflex elicited from left ventricular receptors during occlusion of one coronary artery in the cat. Acta Physiol Scand 88:23–34PubMedGoogle Scholar
  180. Thoren PN (1976) Activation of left ventricular receptors with nonmedullated vagal afferent fibers during occlusion of a coronary artery in the cat. Am J Cardiol 37:1046–1051PubMedGoogle Scholar
  181. Tjen-A-Looi S, H-L Pan, JC Longhurst (1998) Endogenous bradykinin activates ischaemically sensitive cardiac visceral afferents through kinin B2 receptors in cats. J Physiol (Lond) 510:633–641Google Scholar
  182. Tjen-A-Looi S, Fu L-W, Longhurst JC (2002) Xanthine oxidase, but not neutrophils, contribute to activation of cardiac sympathetic afferents during myocardial ischaemia in cats. J Physiol (Lond) 543:327–336Google Scholar
  183. Tokimasa T, Akasu T (1989) Histamine H2 receptor mediates postsynaptic excitation and presynaptic inhibition in submucous plexus neurons of the guinea-pig. Neuroscience 28:735–744PubMedGoogle Scholar
  184. Uchida Y, Murao S (1974) Bradykinin-induced excitation of afferent cardiac sympathetic nerve fibers. Jpn Heart J 15:84–91PubMedGoogle Scholar
  185. Uchida Y, Murao S (1975) Acid-induced excitation of afferent cardiac sympathetic nerve fibers. Am J Physiol 228:27–33PubMedGoogle Scholar
  186. Ustinova EE, Schultz HD (1994) Activation of cardiac vagal afferents in ischemia and reperfusion: prostaglandins vs. oxygen free radicals. Circ Res 74:904–911PubMedGoogle Scholar
  187. Van den Berg EK, Schmitz JM, Benedict CR, Malloy CR, Willerson JT, Dehmer GJ (1989) Transcardiac serotonin concentration is increased in selected patients with limiting angina and complex coronary lesion morphology. Circulation 79:116–124PubMedGoogle Scholar
  188. Van der Vusse GJ, Reneman RS, van Bilsen M (1997) Accumulation of arachidonic acid in ischemic/reperfused cardiac tissue: possible causes and consequences. Prostaglandins Leukot Essent Fatty Acids 57:85–93PubMedGoogle Scholar
  189. Verhoeven AJM, Mommersteeg ME, Akkerman JWN (1984) Quantification of energy consumption in platelets during thrombin-induced aggregation and secretion. Biochem J 221:771–787Google Scholar
  190. Wacker MJ, Tehrani RN, Smoot RL, Orr JA (2002) Thromboxane A2 mimetic evokes a bradycardia mediated by stimulation of cardiac vagal afferent nerves. Am J Physiol Heart Circ Physiol 282:H482–H490PubMedGoogle Scholar
  191. Wacker MJ, Tyburski JB, Ammar CP, Adams MC, Orr JA (2005) Detection of thromboxane A2 receptor mRNA in rabbit nodose ganglion neurons. Neurosci Lett 386:121–126PubMedGoogle Scholar
  192. White JC (1957) Cardiac pain: anatomic pathway and physiologic mechanisms. Circulation 16:644–655PubMedGoogle Scholar
  193. Wilson RF, Wyche K, Christensen BV, Zimmer S, Laxson DD (1990) Effects of adenosine on human coronary arterial circulation. Circulation 82:1595–1606PubMedGoogle Scholar
  194. Wolff AA, Levi R (1988) Ventricular arrhythmias parallel cardiac histamine efflux after coronary artery occlusion in the dog. Agents Actions 25:296–306PubMedGoogle Scholar
  195. Zahner MR, Li D-P, Chen S-R, Pan H-L (2003) Cardiac vanilloid receptor 1-expressing afferent nerves and their role in the cardiogenic sympathetic reflex in rats. J Physiol (Lond) 551(2):515–523Google Scholar
  196. Zucker IH, Cornish KG (1980) Reflex cardiovascular and respiratory effects of serotonin in conscious and anesthetized dogs. Circ Res 47:509–515PubMedGoogle Scholar
  197. Zweier J, Broderick R, Kuppusamy P, Thompson-Gorman S, Lutty GA (1994) Determination of the mechanism of free radical generation in human aortic endothelial cells exposed to anoxia and reoxygenation. J Biol Chem 269:24156–24162PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2009

Authors and Affiliations

  1. 1.Department of Medicine, Department of Physiology and Biophysics, Susan Samueli Center for Integrative Medicine, School of Medicine, C240 Medical Sciences IUniversity of CaliforniaIrvineUSA

Personalised recommendations