Skip to main content

Advertisement

SpringerLink
Log in

Portal blood flow–dependent NO-mediated lymph formation in rat jejunum

  • Organ physiology
  • Published:
Pflügers Archiv - European Journal of Physiology Aims and scope Submit manuscript

Abstract

The higher permeability of the venules in jejunal microcirculation to albumin contributes to the increased mesenteric lymph formation. Recently, we demonstrated that water intake induced serotonin release from enterochromaffin cells in rat jejunum, serotonin of which circulated through the portal vein into blood circulation and then increased the mesenteric lymph formation. The mode of action of serotonin remains unclear. Therefore, we aimed to clarify the mechanisms involved in the regulation of the jejunal lymph formation with permeant albumin in in vivo rat experiments. We investigated the effects of intravenous administration of serotonin or water intake on the jejunal-originated lymph volume and the concentration of albumin in the lymph in the presence or absence of L-NAME. The effects of intravenous administration of L-NAME, nicardipine, A23187, and ML-7 on the lymph formation with permeant albumin were also evaluated. Serotonin or water intake significantly increased the mesenteric lymph volume with permeant albumin in the jejunal microcirculation. The serotonin- and water intake–mediated responses were significantly reduced by the pretreatment with intravenous administration of L-NAME. Intravenous administration of L-NAME itself also decreased significantly the jejunal lymph formation. Administration of A23187 and ML-7 significantly reduced the jejunal lymph formation with permeant albumin. In contrast, administration of nicardipine significantly increased the lymph formation. In conclusion, portal venous blood flow– or serotonin-mediated NO release from venular endothelial cells plays physiologically key roles in the lymph formation in rat jejunum via the extrusion of calcium ions and inactivation of MLCK in endothelial cells.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Data availability

All relevant data are available from the corresponding author on request.

Abbreviations

PSS:

Physiological saline solution

PBS:

Phosphate-buffered saline

NO:

Nitric oxide

L-NAME:

NG-Nitro-L-arginine methyl ester hydrochloride

ML-7:

1-(5-Iodonaphthalene-1-sulfonyl)-1H-hexahydro-1,4-diazepinehydrochloride

ELISA:

Enzyme-linked immunosorbent assay

MLCK:

Myosin light chain kinase

SEM:

Standard errors of the mean

NS:

Not significant

References

  1. Chien S (2007) Mechanotransduction and endothelial cell homeostasis the wisdom of the cell. Am J Physiol Heart Circ Physiol 292:H1209–H1224

    Article  CAS  Google Scholar 

  2. Fukaya Y, Ohhashi T (1996) Acetylcholine- and flow-induced production and release of nitric oxide in arterial and venous endothelial cells. Am J Physiol Heart Circ Physiol 270:H99–H106

    Article  CAS  Google Scholar 

  3. Granger DN, Perry MA, Kvietys PR, Taylor AE (1981) Interstitium-to-blood movement of macromolecules in the absorbing small intestine. Am J Physiol 241:G31–G36

    CAS  PubMed  Google Scholar 

  4. Granger DN, Barrowman JA (1983) Microcirculation of the alimentary tract. Gastroenterology 84:846–868

    Article  CAS  Google Scholar 

  5. Hawkins BT, Egleton RD (2006) Fluorescence imaging of blood-brain barrier disruption. J Neurosci Meth 151:262–267

    Article  CAS  Google Scholar 

  6. Huang Q, Yuan Y (1997) Interaction of PKC and NOS in signal transduction of microvascular hyperpermeability. Am J Physiol Heart Circ Physiol 273:H2442–H2451

    Article  CAS  Google Scholar 

  7. Joris I, Majno G, Corey EJ, Lewis RA (1987) The mechanism of vascular leakage induced by leukotriene E4 endothelial contraction. Am J Pathol 126:19–24

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Kawai Y, Ajima K, Nagai T, Yokoyama Y, Kaidoh M, Seto E, Honda T, Ohhashi T (2015) Abdominal respiration induces hemodilution and related reduction in ADH concentration. Lymphatic Res Biol 13:202–207

    Article  CAS  Google Scholar 

  9. Kawai Y, Yokoyama Y, Kaidoh M, Ohhashi T (2010) Shear stress-induced ATP-mediated endothelial constitutive nitric oxide synthase expression in human lymphatic endothelial cells. Am J Physiol Cell Physiol 298:C647–C655

    Article  CAS  Google Scholar 

  10. Kajihara R, Amari K, Arai N, Nagashio S, Hayashi M, Watanabe-Asaka T, Kaidoh M, Yokoyama Y, Maejima D, Kawai Y, Ohhashi T (2021) Water intake releases serotonin from enterochromaffin cells in rats jejunal villi. Pflügers Arch Eur J Physiol 473:921–936

    Article  CAS  Google Scholar 

  11. Michel AD, Whiting RL (1989) Cellular action of nicardipine. AM J Cardiol 64:3H-7H

    Article  CAS  Google Scholar 

  12. Michel CC, Kendal S (1997) Differing effects of histamine and serotonin on microvascular pearmeabilty in anesthetized rats. J Physiol (Lond) 501:657–662

    Article  CAS  Google Scholar 

  13. Mizuno R, Ohhashi T (1995) 5-Hydroxytryptamine-induced nitric oxide-dependent relaxation in isolated strips of monkey popliteal lymph nodes. Am J Physiol Heart Circ Physiol 268:H2246–H2251

    Article  CAS  Google Scholar 

  14. Nagashio S, Ajima K, Maejima D, Sanjo H, Kajihara R, Hayashi M, Watanabe-Asaka T, Kaidoh M, Yokoyama Y, Taki S, Kawai Y, Ohhashi T (2019) Water intake increases mesenteric lymph flow and the total flux of albumin, long-chain fatty acids, and IL-22 in rats: new concept of absorption in jejunum. Am J Physiol Gastrointest and Liver Physiol 316:G155–G165

    Article  CAS  Google Scholar 

  15. Ohhashi T, Kawai Y, Azuma T (1978) The response of lymphatic smooth muscles to vasoactive substances. Pfluegers Arch 375:183–188

    Article  CAS  Google Scholar 

  16. Ohhashi T, Azuma T, Sakaguchi M (1980) Active and passive mechanical characteristics of bovine mesenteric lymphatics. Am J Physiol 239:H88–H95

    CAS  PubMed  Google Scholar 

  17. Ohhashi, T ( 1987) Regulation of motility of small collecting lymphatics. In: Advances in microcirculation; Staub NC, Hargens AR, eds, Basel, Karger AG, pp 171–183

  18. Ohhashi T, Yokoyama S (1994) Nitric oxide and the lymphatic system. (Review) Jpn J Physiol 44: 327–342

  19. Ohhashi T, Mizuno R, Ikomi F, Kawai Y (2005) Current topics of physiology and pharmacology in the lymphatic system. Pharmacol Ther 105:165–188

    Article  CAS  Google Scholar 

  20. Renkin EM (1986) Some consequences of capillary permeability to macromolecules: Starling’s hypothesis reconsidered. Am J Physiol 250:H706–H710

    CAS  PubMed  Google Scholar 

  21. Shirasawa Y, Ikomi F, Ohhashi T (2000) Physiological roles of endogenous nitric oxide in lymphatic pump activity of rat mesentery in vivo. Am J Physiol 278:G551–G556

    CAS  Google Scholar 

  22. Simmonds WJ (1955) Some observations on the increase in thoracic duct lymph flow during intestinal absorption of fat in unanaesthetized rats. Aust J exp Biol med Sci 33:305–313

    Article  CAS  Google Scholar 

  23. Taylor AE (1981) Capillary fluid filtration Starling forces and lymph flow. Circ Res 49:557–575

    Article  CAS  Google Scholar 

  24. Thompson MP, Williamson DH (1976) The ability of the calcium ionophore A-23187 to mimic some of the effects of adrenaline on the metabolism of rat submaxillary gland. FEEB Lett 62:208–211

    Article  CAS  Google Scholar 

  25. Tsunemoto H, Ikomi F, Ohhashi T (2003) Flow-induced nitric oxide-mediated dilatation in pressurized canine thoracic duct. Jpn J Physiol 53:157–163

    Article  CAS  Google Scholar 

  26. Turlapaty P, Vary R, Kaplan JA (1989) Nicardipine, a new intravenous calcium antagonist: a review of its pharmacology, pharmacokinetics, and perioperative applications. J Cardiothorac Anesth 3:344–355

    Article  CAS  Google Scholar 

  27. Yamamoto K, Shimizu N, Obi S, Kumagaya S, Taketani Y, Kamiya A, Ando J (2007) Involvement of cell surface ATP synthase in flow-induced ATP release by vascular endothelial cells. Am J Physiol Heart Circ Physiol 293:H1646–H1653

    Article  CAS  Google Scholar 

  28. Yoffey JM, Courtice FC (1970) Lymphatics and lymph circulation. Academic Press, London

    Google Scholar 

  29. Yuan SY (2000) Signal transduction pathways in enhanced microvascular permeability. Microcirculation 6:395–403

    Article  Google Scholar 

  30. Yuan SY, Wu MK, Ustinova EE, Guo M, Tinsley JH, De Lanerolle P, Xu W (2002) Myosin light chain phosphorylation in neutrophil-stimulated coronary microvascular leakage. Circ Res 90:1214–1221

    Article  CAS  Google Scholar 

  31. Yuan Y, Chilian WM, Granger HJ, Zawieja DC (1993) Permeability to albumin in isolated coronary venules. Am J Physiol 265:H543–H552

    CAS  PubMed  Google Scholar 

  32. Yuan Y, Huang Q, Wu HM (1997) Myosin light chain phosphorylation: modulation of basal and agonist-stimulated venular permeability. Am J Physiol Heart Circ Physiol 272:H1437–H1443

    Article  CAS  Google Scholar 

  33. Wu NZ, Baldin AL (1992) Transient venular permeability increase and endothelial gap formation induced by histamine. Am J Physiol 262:H1238–H1247

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank Editage for English language editing in support of non-native English speakers. The Department of Innovation of Medical and Health Sciences Research at Shinshu University School of Medicine has been established and supported financially by the donation of BOURBON, Co., Ltd, Kashiwazaki, Niigata, Japan, and Aizawa Hospital, Matsumoto, Nagano, Japan.

Funding

The authors declare that this study received funding from BOURBON Co. Ltd. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article, or the decision to submit it for publication.

Author information

Authors and Affiliations

  1. Department of Innovation of Medical and Health Sciences Research, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621, Japan

    Kei Amari, Ryo Kajihara, Nariaki Arai, Moyuru Hayashi, Tomomi Watanabe-Asaka, Maki Kaidoh, Yumiko Yokoyama, Kumiko Ajima, Daisuke Maejima, Yoshiko Kawai & Toshio Ohhashi

  2. Department of Dentistry and Oral Surgery, Shinshu University School of Medicine, Matsumoto, Japan

    Kei Amari & Ryo Kajihara

  3. Department of Anesthesiology and Resuscitology, Shinshu University School of Medicine, Matsumoto, Japan

    Nariaki Arai

  4. Division of Physiology, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, Sendai, Japan

    Moyuru Hayashi, Tomomi Watanabe-Asaka & Yoshiko Kawai

Authors
  1. Kei Amari
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ryo Kajihara
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nariaki Arai
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Moyuru Hayashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Tomomi Watanabe-Asaka
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Maki Kaidoh
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yumiko Yokoyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Kumiko Ajima
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Daisuke Maejima
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Yoshiko Kawai
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Toshio Ohhashi
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

T.O. wrote the manuscript, designed the experiments, and analyzed the data. Y.K., M.H., and T-W-A. designed the experiments, analyzed the data, and revised the manuscript. K.A., R.K., N.A., K.A., D.M., Y.Y., and M.K. performed the experiments, and analyzed data. All authors approved the final version of the manuscript and accepted for the publication of this manuscript.

Corresponding author

Correspondence to Toshio Ohhashi.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Amari, K., Kajihara, R., Arai, N. et al. Portal blood flow–dependent NO-mediated lymph formation in rat jejunum. Pflugers Arch - Eur J Physiol 474, 541–551 (2022). https://doi.org/10.1007/s00424-022-02670-2

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00424-022-02670-2

Keywords

Search

Navigation