Advertisement

Cell and Tissue Research

, Volume 379, Issue 2, pp 373–387 | Cite as

Contractile elements and their sympathetic regulations in the pig urinary bladder: a species and regional comparative study

  • Retsu MitsuiEmail author
  • Ken Lee
  • Aoi Uchiyama
  • Shunta Hayakawa
  • Fumio Kinoshita
  • Shunichi Kajioka
  • Masatoshi Eto
  • Hikaru Hashitani
Regular Article

Abstract

Contractile behaviour of the urinary bladder and its sympathetic inhibition during storage phases are not well understood. Here, we explore muscularis mucosae (MM) as a predominant mucosal contractile element and the capability of sympathetic nerves to relax detrusor smooth muscle (DSM) or MM. Distribution of α-smooth muscle actin (α-SMA)-immunoreactive cells was compared in pig, human, guinea pig, rat and mouse bladders by immunohistochemistry, while contractility of the bladder mucosa was compared in these species by isometric tension recordings. In pig, human and guinea pig bladders, DSM and MM located in the lamina propria expressed α-SMA immunoreactivity, while both rat and mouse bladders lacked a MM. Consistent with this presence or absence of MM, bladder mucosa of pig, human and guinea pig but not rat and mouse developed spontaneous phasic contractions (SPCs). Distribution of tyrosine hydroxylase (TH)-immunoreactive sympathetic nerve fibres was compared in pig DSM, MM, trigone and urethra, as were their sympathetic nerve-evoked contractile/relaxing responses examined. In pig DSM or MM, where TH-immunoreactive sympathetic fibres exclusively projected to the vasculature, sympathetic relaxations were difficult to demonstrate. In contrast, sympathetic contractions were invariably evoked in pig trigone and urethra where the smooth muscle cells receive TH-immunoreactive sympathetic innervations. Thus, SPCs of bladder mucosa appear to predominantly arise from the MM displaying species differences. Despite the currently accepted concept of sympathetic nerve-mediated DSM relaxation during the storage phase, it is unlikely that neurally released noradrenaline acts on β-adrenoceptors to relax either DSM or MM due to the anatomical lack of sympathetic innervation.

Keywords

Urinary bladder Muscularis mucosae Trigone Urethra Smooth muscle Sympathetic nerve 

Abbreviations

α-SMA

α-Smooth muscle actin

DSM

Detrusor smooth muscle

EFS

Electrical filed stimulation

MM

Muscularis mucosae

PSS

Physiological salt solution

SMC

Smooth muscle cell

SPC

Spontaneous phasic contraction

TH

Tyrosine hydroxylase

Notes

Acknowledgements

The authors wish to thank Dr. Richard Lang (Monash University) for his critical reading of the manuscript and are also grateful to Drs Akito Yamaguchi and Shinji Kono (Harasanshin Hospital) for providing human bladder specimens.

Funding

The present study was partly supported by Grant-in-Aid for Young Scientists (B) (No. 16K19361) from Japan Society for Promotion of the Science (JSPS) to R.M. and Grant-in-Aid for Scientific Research (C) (No. 17K11187) from JSPS to H.H.

Compliance with ethical statements

Conflict of interest

The authors declare that there is no conflict of interest.

Ethical approval

The experimental protocols used in the present study were approved by the animal experimentation ethics committee at Nagoya City University Graduate School of Medical Sciences (No. H-28M-07) and the Ethics Committees of the Graduate School of Medical Sciences, Kyushu University and Harasanshin Hospital (No. 28-54). All procedures performed in studies involving human participants were in accordance with the 1964 Helsinki declaration and its later amendments.

Informed consent

All subjects gave written informed consent.

References

  1. Alm P, Elmér M (1975) Adrenergic and cholinergic innervation of the rat urinary bladder. Acta Physiol Scand 94:36–45PubMedGoogle Scholar
  2. Andersson KE (2017) On the site and mechanism of action of β3-adrenoceptor agonists in the bladder. Int Neurourol J 21:6–11PubMedPubMedCentralGoogle Scholar
  3. Andersson KE, Mattiasson A, Sjögren C (1983) Electrically induced relaxation of the noradrenaline contracted isolated urethra from rabbit and man. J Urol 129:210–214PubMedGoogle Scholar
  4. Andersson KE, Boedtkjer DB, Forman A (2017) The link between vascular dysfunction, bladder ischemia, and aging bladder dysfunction. Ther Adv Urol 9:11–27PubMedGoogle Scholar
  5. Andersson KE, Choudhury N, Cornu JN, Huang M, Korstanje C, Siddiqui E, Van Kerrebroeck P (2018) The efficacy of mirabegron in the treatment of urgency and the potential utility of combination therapy. Ther Adv Urol 10:243–256PubMedPubMedCentralGoogle Scholar
  6. Brading AF (1997) A myogenic basis for the overactive bladder. Urology 50:57–67PubMedGoogle Scholar
  7. Brading AF (2006) Spontaneous activity of lower urinary tract smooth muscles: correlation between ion channels and tissue function. J Physiol 570:13–22PubMedPubMedCentralGoogle Scholar
  8. De Groat WC, Saum WR (1972) Sympathetic inhibition of the urinary bladder and of pelvic ganglionic transmission in the cat. J Physiol 220:297–314PubMedPubMedCentralGoogle Scholar
  9. De Groat WC, Theobald RJ (1976) Reflex activation of sympathetic pathways to vesical smooth muscle and parasympathetic ganglia by electrical stimulation of vesical afferents. J Physiol 259:223–237PubMedPubMedCentralGoogle Scholar
  10. Dixon JS, Gosling JA (1983) Histology and fine structure of the muscularis mucosae of the human urinary bladder. J Anat 136:265–271PubMedPubMedCentralGoogle Scholar
  11. Drake MJ, Fry CH, Hashitani H, Kirschner-Hermanns R, Rahnama’i MS, Speich JE, Tomoe H, Kanai AJ, McCloskey KD (2018) What are the origins and relevance of spontaneous bladder contractions? ICI-RS 2017. Neurourol Urodyn 37:S13–S19PubMedPubMedCentralGoogle Scholar
  12. Drake MJ, Harvey IJ, Gillespie JI (2003) Autonomous activity in the isolated guinea pig bladder. Exp Physiol 88:19–30PubMedGoogle Scholar
  13. Drake MJ, Harvey IJ, Gillespie JI, Van Duyl WA (2005) Localized contractions in the normal human bladder and in urinary urgency. BJU Int 95:1002–1005PubMedGoogle Scholar
  14. Fowler CJ, Griffiths D, de Groat WC (2008) The neural control of micturition. Nat Rev Neurosci 9:453–466PubMedPubMedCentralGoogle Scholar
  15. Fry CH, Vahabi B (2016) The role of the mucosa in normal and abnormal bladder function. Basic Clin Pharmacol Toxicol 119:57–62PubMedPubMedCentralGoogle Scholar
  16. Gabella G, Uvelius B (1990) Urinary bladder of rat: fine structure of normal and hypertrophic musculature. Cell Tissue Res 262:67–79PubMedGoogle Scholar
  17. Gevaert T, Vanstreels E, Daelemans D, Franken J, Van Der Aa F, Roskams T, De Ridder D (2014) Identification of different phenotypes of interstitial cells in the upper and deep lamina propria of the human bladder dome. J Urol 19:1555–1563Google Scholar
  18. Gosling JA, Dixon JS, Jen PY (1999) The distribution of noradrenergic nerves in the human lower urinary tract. A review Eur Urol 36(Suppl 1):23–30PubMedGoogle Scholar
  19. Gosling JA, Dixon JS, Lendon RG (1977) The autonomic innervation of the human male and female bladder neck and proximal urethra. J Urol 118:302–305PubMedGoogle Scholar
  20. Heppner TJ, Hennig GW, Nelson MT, Vizzard MA (2017) Rhythmic calcium events in the lamina propria network of the urinary bladder of rat pups. Front Syst Neurosci 11(87):1–16Google Scholar
  21. Heppner TJ, Layne JJ, Pearson JM, Sarkissian H, Nelson MT (2011) Unique properties of muscularis mucosae smooth muscle in guinea pig urinary bladder. Am J Phys Regul Integr Comp Phys 301:R351–3R62Google Scholar
  22. Heppner TJ, Tykocki NR, Hill-Eubanks D, Nelson MT (2016) Transient contractions of urinary bladder smooth muscle are drivers of afferent nerve activity during filling. J Gen Physiol 147:323–335PubMedPubMedCentralGoogle Scholar
  23. Ikeda Y, Fry C, Hayashi F, Stolz D, Griffiths D, Kanai A (2007) Role of gap junctions in spontaneous activity of the rat bladder. Am J Physiol Ren Physiol 293:F1018–F1025Google Scholar
  24. Isogai A, Lee K, Mitsui R, Hashitani H (2016) Functional coupling of TRPV4 channels and BK channels in regulating spontaneous contractions of the guinea pig urinary bladder. Pflugers Arch 468:1573–1585PubMedGoogle Scholar
  25. Klarskov P (1987) Non-cholinergic, non-adrenergic nerve-mediated relaxation of pig and human detrusor muscle in vitro. Br J Urol 59:414–419PubMedGoogle Scholar
  26. Klarskov P, Gerstenberg TC, Ramirez D, Hald T (1983) Non-cholinergic, non-adrenergic nerve mediated relaxation of trigone, bladder neck and urethral smooth muscle in vitro. J Urol 129:848–850PubMedGoogle Scholar
  27. Kushida N, Fry CH (2016) On the origin of spontaneous activity in the bladder. BJU Int 17:982–992Google Scholar
  28. Larsen JJ, Nordling J, Christensen B (1978) Sympathetic innervation of the urinary bladder and urethral muscle in the pig. Acta Physiol Scand 104:485–490PubMedGoogle Scholar
  29. Lee K, Isogai A, Antoh M, Kajioka S, Eto M, Hashitani H (2018) Role of K+ channels in regulating spontaneous activity in the muscularis mucosae of guinea pig bladder. Eur J Pharmacol 818:30–37PubMedGoogle Scholar
  30. Lee K, Mitsui R, Kajioka S, Naito S, Hashitani H (2016) Role of PTHrP and sensory nerve peptides in regulating contractility of muscularis mucosae and detrusor smooth muscle in the guinea pig bladder. J Urol 196:1287–1294PubMedGoogle Scholar
  31. McCarthy CJ, Zabbarova IV, Brumovsky PR, Roppolo JR, Gebhart GF, Kanai AJ (2009) Spontaneous contractions evoke afferent nerve firing in mouse bladders with detrusor overactivity. J Urol 181:1459–1466PubMedPubMedCentralGoogle Scholar
  32. Mitsui R, Hashitani H (2013) Immunohistochemical characteristics of suburothelial microvasculature in the mouse bladder. Histochem Cell Biol 140:189–200PubMedGoogle Scholar
  33. Moro C, Chess-Williams R (2012) Non-adrenergic, non-cholinergic, non-purinergic contractions of the urothelium/lamina propria of the pig bladder. Auton Autacoid Pharmacol 32:53–59PubMedGoogle Scholar
  34. Moro C, Leeds C, Chess-Williams R (2012) Contractile activity of the bladder urothelium/lamina propria and its regulation by nitric oxide. Eur J Pharmacol 674:445–449PubMedGoogle Scholar
  35. Moro C, Tajouri L, Chess-Williams R (2013) Adrenoceptor function and expression in bladder urothelium and lamina propria. Urology 81:211.e1-7PubMedGoogle Scholar
  36. Moro C, Uchiyama J, Chess-Williams R (2011) Urothelial/lamina propria spontaneous activity and the role of M3 muscarinic receptors in mediating rate responses to stretch and carbachol. Urology 78:1442.e9–1442.15Google Scholar
  37. Ouslander JG (2004) Management of overactive bladder. N Engl J Med 350:786–799PubMedGoogle Scholar
  38. Persson K, Andersson KE (1992) Nitric oxide and relaxation of pig lower urinary tract. Br J Pharmacol 106:416–422PubMedPubMedCentralGoogle Scholar
  39. Ro JY, Ayala AG, El-Naggar A (1987) Muscularis mucosa of urinary bladder. Importance for staging and treatment. Am J Surg Pathol 11:668–673PubMedGoogle Scholar
  40. Robertson AS (1999) Behaviour of the human bladder during natural filling: the Newcastle experience of ambulatory monitoring and conventional artificial filling cystometry. Scand J Urol Nephrol Suppl 201:19–24PubMedGoogle Scholar
  41. Sadananda P, Chess-Williams R, Burcher E (2008) Contractile properties of the pig bladder mucosa in response to neurokinin A: a role for myofibroblasts. Br J Pharmacol 153:1465–1473PubMedPubMedCentralGoogle Scholar
  42. Shimizu Y, Mochizuki S, Mitsui R, Hashitani H (2014) Neurohumoral regulation of spontaneous constrictions in suburothelial venules of the rat urinary bladder. Vasc Pharmacol 60:84–94Google Scholar
  43. Sibley GNA (1984) Comparison of spontaneous and nerve-mediated activity in bladder muscle from man, pig and rabbit. J Physiol 354:431–443PubMedPubMedCentralGoogle Scholar
  44. Speakman MJ, Walmsley D, Brading AF (1988) An in vitro pharmacological study of the human trigone--a site of non-adrenergic, non-cholinergic neurotransmission. Br J Urol 61:304–309PubMedGoogle Scholar
  45. Sui G, Fry CH, Montgomery B, Roberts M, Wu R, Wu C (2014) Purinergic and muscarinic modulation of ATP release from the urothelium and its paracrine actions. Am J Physiol Ren Physiol 306:F286–F298Google Scholar
  46. Vahabi B, Drake MJ (2015) Physiological and pathophysiological implications of micromotion activity in urinary bladder function. Acta Physiol (Oxford) 213:360–370Google Scholar
  47. Vahabi B, Sellers DJ, Bijos DA, Drake MJ (2013) Phasic contractions in urinary bladder from juvenile versus adult pigs. PLoS One 8:e58611PubMedPubMedCentralGoogle Scholar
  48. Wakabayashi Y, Makiura Y, Tomoyoshi T, Kitahama K, Maeda T (1993) Immuno-electron microscopic study of tyrosine hydroxylase in the cat urinary bladder and proximal urethra. J Auton Nerv Syst 44:243–252PubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Retsu Mitsui
    • 1
    Email author
  • Ken Lee
    • 2
  • Aoi Uchiyama
    • 1
  • Shunta Hayakawa
    • 1
  • Fumio Kinoshita
    • 3
  • Shunichi Kajioka
    • 4
  • Masatoshi Eto
    • 2
  • Hikaru Hashitani
    • 1
  1. 1.Department of Cell PhysiologyNagoya City University Graduate School of Medical SciencesNagoyaJapan
  2. 2.Department of Urology, Graduate School of Medical SciencesKyushu UniversityFukuokaJapan
  3. 3.Department of Anatomic Pathology, Graduate School of Medical SciencesKyushu UniversityFukuokaJapan
  4. 4.Department of Applied Urology and Molecular MedicineKyushu UniversityFukuokaJapan

Personalised recommendations