Skip to main content
SpringerLink
Log in

Myogenic tone in mouse mesenteric arteries: evidence for P2Y receptor-mediated, Na+, K+, 2Cl− cotransport-dependent signaling

  • Original Paper
  • Published:
Purinergic Signalling Aims and scope Submit manuscript

Abstract

This study examines the action of agonists and antagonists of P2 receptors on mouse mesenteric artery contractions and the possible involvement of these signaling pathways in myogenic tone (MT) evoked by elevated intraluminal pressure. Both ATP and its non-hydrolyzed analog α,β-ATP triggered transient contractions that were sharply decreased in the presence of NF023, a potent antagonist of P2X1 receptors. In contrast, UTP and UDP elicited sustained contractions which were suppressed by MRS2567, a selective antagonist of P2Y6 receptors. Inhibition of Na+, K+, 2Cl− cotransport (NKCC) with bumetanide led to attenuation of contractions in UTP- but not ATP-treated arteries. Both UTP-induced contractions and MT were suppressed by MRS2567 and bumetanide but were insensitive to NF023. These data implicate a P2Y6-mediated, NKCC-dependent mechanism in MT of mesenteric arteries. The action of heightened intraluminal pressure on UTP release from mesenteric arteries and its role in the triggering of P2Y6-mediated signaling should be examined further.

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
Fig. 7

Similar content being viewed by others

References

  1. Bayliss WM (1902) On the local reactions of the arterial wall to changes of internal pressure. J Physiol 28:220–231

    PubMed  CAS  Google Scholar 

  2. Uchida E, Bohr DF (1969) Myogenic tone in isolated perfused vessels. Occurrence among vascular beds and along vascular trees. Circ Res 25:549–555

    PubMed  CAS  Google Scholar 

  3. Davis MJ, Hill MA (1999) Signaling mechanisms underlying the vascular myogenic response. Physiol Rev 79:387–423

    PubMed  CAS  Google Scholar 

  4. Zhang J, Lee MY, Cavalli M et al (2005) Sodium pump a2 subunits control myogenic tone and blood pressure in mice. J Physiol 569:243–256. doi:10.1113/jphysiol.2005.091801

    Article  PubMed  CAS  Google Scholar 

  5. Murphy TV (2007) I don't need this pressure on; src-family kinases, ERK 1/2 kinase and mechanotransduction in arteries. J Hypertens 25:1791–1793. doi:10.1097/HJH.0b013e3282ef45f9

    Article  PubMed  CAS  Google Scholar 

  6. Hughes JM, Bund SJ (2002) Arterial myogenic properties of the spontaneously hypertensive rats. Exp Physiol 87:527–534. doi:10.1113/eph8702399

    Article  PubMed  Google Scholar 

  7. Loutzenhiser R, Griffin K, Williamson G et al (2006) Renal autoregulation: new perspectives regarding the protective and regulatory roles of the underlying mechanisms. Am J Physiol Regul Integr Comp Physiol 290:R1153–R1167. doi:10.1152/ajpregu.00402.2005

    PubMed  CAS  Google Scholar 

  8. Zhang J, Berra-Romani R, Sinnegger-Brauns MJ et al (2007) Role of Cav1.2 L-type Ca2+ channels in vascular tone: effects of nifedipine and Mg2+. Am J Physiol Heart Circ Physiol 292:H415–H425. doi:10.1152/ajpheart.01214.2005

    Article  PubMed  CAS  Google Scholar 

  9. Lucchesi PA, Sabri A, Belmadani S et al (2004) Involvement of metalloproteinases 2/9 in epidermal growth factor receptor transactivation in pressure-induced myogenic tone in mouse mesenteric resistance arteries. Circulation 110:3587–3593. doi:10.1161/01.CIR.0000148780.36121.47

    Article  PubMed  CAS  Google Scholar 

  10. Schubert R, Lidington D, Bolz S-S (2008) The emerging role of Ca2+ sensitivity regulation in promoting myogenic vasoconstriction. Cardiovasc Res 77:8–18

    PubMed  CAS  Google Scholar 

  11. Hill MA, Davis MJ, Meininger GA et al (2006) Arteriolar myogenic signaling mechanisms: implications for local vascular functions. Clin Hemorheol Microcirc 34:67–79

    PubMed  Google Scholar 

  12. Groulx N, Boudreault F, Orlov SN et al (2006) Membrane reserves and hypotonic cell swelling. J Membr Biol 214:43–56. doi:10.1007/s00232-006-0080-8

    Article  PubMed  CAS  Google Scholar 

  13. Tatur S, Groulx N, Orlov SN et al (2007) Ca2+-dependent ATP release from A549 cells involves synergic autocrine stimulation by coreleased uridine nucleotides. J Physiol 584:419–435. doi:10.1113/jphysiol.2007.133314

    Article  PubMed  CAS  Google Scholar 

  14. Burnstock G (2007) Physiology and pathophysiology of purinergic neurotransmission. Physiol Rev 87:659–797. doi:10.1152/physrev.00043.2006

    Article  PubMed  CAS  Google Scholar 

  15. Zhao Y, Migita K, Sato C et al (2007) Endoplasmic reticulum is a key organella in bradykinin-triggered ATP-release from cultured smooth muscle cells. J Pharmacol Sci 105:57–65. doi:10.1254/jphs.FP0070865

    Article  PubMed  CAS  Google Scholar 

  16. Erlinge D, Burnstock G (2008) P2 receptors in cardiovascular regulation and disease. Purinergic Signal 4:1–20. doi:10.1007/s11302-007-9078-7

    Article  PubMed  CAS  Google Scholar 

  17. Burnstock G (2006) Vessel tone and remodeling. Nat Med 12:16–17. doi:10.1038/nm0106-16

    Article  PubMed  CAS  Google Scholar 

  18. Gamba G (2005) Molecular physiology and pathophysiology of electroneutral cation-chloride cotransporters. Physiol Rev 85:423–493. doi:10.1152/physrev.00011.2004

    Article  PubMed  CAS  Google Scholar 

  19. Chipperfield AR, Harper AA (2001) Chloride in smooth muscle. Prog Biophys Mol Biol 74:175–221. doi:10.1016/S0079-6107(00)00024-9

    Article  Google Scholar 

  20. Kreye VA, Bauer PK, Villhauer I (1981) Evidence for furosemide-sensitive active chloride transport in vascular smooth muscle. Eur J Pharmacol 73:91–95. doi:10.1016/0014-2999(81)90150-3

    Article  PubMed  CAS  Google Scholar 

  21. Davis JPL, Chipperfield AR, Harper AA (1993) Accumulation of intracellular chloride by (Na–K–Cl) cotransport in rat arterial smooth muscle is enhanced in deoxycorticosterone acetate (DOCA)/salt hypertension. J Mol Cell Cardiol 25:233–237. doi:10.1006/jmcc.1993.1029

    Article  PubMed  CAS  Google Scholar 

  22. Anfinogenova YJ, Baskakov MB, Kovalev IV et al (2004) Cell-volume-dependent vascular smooth muscle contraction: role of Na+, K+, 2Cl- cotransport, intracellular Cl- and L-type Ca2+ channels. Pflugers Arch 449:42–55. doi:10.1007/s00424-004-1316-z

    Article  PubMed  CAS  Google Scholar 

  23. Barthelmebs M, Stephan D, Fontaine C et al (1994) Vascular effects of loop diuretics: an in vivo and in vitro study in the rat. Naunyn Schmiedebergs Arch Pharmacol 349:209–216. doi:10.1007/BF00169839

    Article  PubMed  CAS  Google Scholar 

  24. Lavallee SL, Iwamoto LM, Claybaugh JR et al (1997) Furosemide-induced airway relaxation in guinea pigs: relation to Na-K-2Cl cotransporet function. Am J Physiol 273:L211–L216

    PubMed  CAS  Google Scholar 

  25. Tian R, Aalkjaer C, Andreasen F (1990) Mechanisms behind the relaxing effect of furosemide on the isolated rabbit ear artery. Pharmacol Toxicol 67:406–410

    Article  PubMed  CAS  Google Scholar 

  26. Akar F, Skinner E, Klein JD et al (1999) Vasoconstrictors and nitrovasodilators reciprocally regulate the Na+-K+-2Cl- cotransporter in rat aorta. Am J Physiol 276:C1383–C1390

    PubMed  CAS  Google Scholar 

  27. Garg P, Martin C, Elms SC et al (2007) Effect of the Na–K–2Cl cotransporter NKCC1 on systematic blood pressure and smooth muscle tone. Am J Physiol Heart Circ Physiol 292:H2100–H2105. doi:10.1152/ajpheart.01402.2006

    Article  PubMed  CAS  Google Scholar 

  28. Palacios J, Espinoza F, Munita C et al (2006) Na+–K+–2Cl− cotransporter is implicated in gender differences in the response of the rat aorta to phenylephrine. Br J Pharmacol 148:964–972. doi:10.1038/sj.bjp. 0706818

    Article  PubMed  CAS  Google Scholar 

  29. Kovalev IV, Baskakov MB, Medvedev MA et al (2008) Na+, K+, 2Cl− cotransport and chloride permeability of the cell membrane in mezaton and histamine regulation of electrical and contractile activity in smooth muscle cells from the guinea pig ureter. Russ Phys J 93:306–317

    Google Scholar 

  30. Stanke F, Devillier P, Breant D et al (1998) Furosemide inhibits angiotensin II-induced contraction on human vascular smooth muscle. Br J Clin Pharmacol 46:571–575. doi:10.1046/j.1365-2125.1998.00820.x

    Article  PubMed  CAS  Google Scholar 

  31. Stanke-Labesque F, Craciwski JL, Bedouch P et al (2000) Furosemide inhibits thrombaxane A2-induced contraction in isolated human internal artery and saphenous vein. J Cardiovasc Pharmacol 35:531–537. doi:10.1097/00005344-200004000-00003

    Article  PubMed  CAS  Google Scholar 

  32. Wang X, Breaks J, Loutzenhiser K et al (2007) Effects of inhibition of the Na+/K+/2Cl− cotransporter on myogenic and angiotensin II responses of the rat afferent arteriole. Am J Physiol Renal Physiol 292:F999–F1006. doi:10.1152/ajprenal.00343.2006

    Article  PubMed  CAS  Google Scholar 

  33. Mozhayeva MG, Bagrov YY (1995) The inhibitory effects of furosemide on Ca2+ influx pathways associated with oxytocin-induced contractions of rat myometrium. Gen Physiol Biophys 14:427–436

    PubMed  CAS  Google Scholar 

  34. Mozhayeva MG, Bagrov YY, Ostretsova IB et al (1994) The effect of furosemide on oxytocin-induced contractions of the rat myometrium. Exp Physiol 79:661–667

    PubMed  CAS  Google Scholar 

  35. von Kügelgen I (2006) Pharmacological profiles of cloned mammalian P2Y-receptor subtypes. Pharmacol Ther 110:415–4322. doi:10.1016/j.pharmthera.2005.08.014

    Article  Google Scholar 

  36. Nori SL, Fumagalli L, Bo X et al (1998) Coexpression of mRNAs for P2X1, P2X2 and P2X4 receptors in rat vascular smooth muscle: an in situ hybridization and RT-PCR study. J Vasc Res 35:179–185. doi:10.1159/000025582

    Article  PubMed  CAS  Google Scholar 

  37. Phillips JK, McLean AL, Hill CE (1998) Receptors involved in nerve-mediated vasoconstriction in small arteries of the rat mesentery. Br J Pharmacol 124:1403–1412. doi:10.1038/sj.bjp.0701976

    Article  PubMed  CAS  Google Scholar 

  38. Volchanova L, Arvidsson U, Riedl M et al (1996) Differential distribution of two ATP-gated ion channels (P2X receptors) determined by immunohistochemistry. Proc Natl Acad Sci USA 93:7617–7622

    Google Scholar 

  39. Vial C, Evans RJ (2002) P2X1 receptor-deficient mice establish the native P2X receptor and P2Y6-like receptor arteries. Mol Pharmacol 62:1438–1445. doi:10.1124/mol.62.6.1438

    Article  PubMed  CAS  Google Scholar 

  40. Rayment SJ, Latif ML, Ralevic V et al (2007) Evidence for the expression of multiple uracil nucleotide-stimulated P2 receptors coupled to smooth muscle contraction in porcine isolated arteries. Br J Pharmacol 150:604–612. doi:10.1038/sj.bjp. 0707120

    Article  PubMed  CAS  Google Scholar 

  41. Roberts JA, Vial C, Digby HR et al (2006) Molecular properties of P2X receptors. Pfluger Arch 452:486–500. doi:10.1007/s00424-006-0073-6

    Article  CAS  Google Scholar 

  42. Egan TM, Samways DSK, Li Z (2006) Biohysics of P2X receptors. Pflugers Arch 452:501–512. doi:10.1007/s00424-006-0078-1

    Article  PubMed  CAS  Google Scholar 

  43. Cipleu CD, Palant CE, Sanders KM et al (2002) Separation of two Cl− currents in cultured human and murine mesangial cells: biphysical and pharmacological characteristics of ICl.vol. and ICl. Ca. J.Vasc Res 39:426–436

    Article  PubMed  CAS  Google Scholar 

  44. Juul B, Plesner L, Aalkjaer C (1992) Effects of ATP and UTP on [Ca2+]i, membrane potential and force in isolated rat small arteries. J Vasc Res 29:385–395. doi:10.1159/000158955

    Article  PubMed  CAS  Google Scholar 

  45. Bar I, Guns PJ, Metallo J et al (2008) Knockout mice reveal a role for P2Y6 receptor in macrophages, endothelial cells, and vascular smooth muscle cells. Mol Pharmacol 74:777–784. doi:10.1124/mol.108.046904

    Article  PubMed  CAS  Google Scholar 

  46. Shibata K, Morita Y, Abe S et al (1999) Apyrase from pea stems: isolation, purification, characterization and identification of a NTPase from the cytoskeleton fraction of pea stem tissue. Plant Physiol Biochem 37:881–888. doi:10.1016/S0981-9428(99)00102-3

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by grants from the Canadian Institutes of Health Research and the Heart and Stroke Foundation of Canada. The editorial assistance of Ovid Da Silva (irtc.inc@hotmail.com) is acknowledged.

Author information

Authors and Affiliations

  1. Research Centre, University of Montreal Hospital Centre (CRCHUM), Technopôle Angus, Moscow, Russia

    Svetlana V. Koltsova, Julie L. Lavoie, Johanne Tremblay, Ryszard Grygorczyk, Pavel Hamet & Sergei N. Orlov

  2. Institute of General Pathology and Pathophysiology, Russian Academy of Medical Sciences, Moscow, Russia

    Svetlana V. Koltsova & Sergei N. Orlov

  3. Faculty of Biology, M.V. Lomonosov Moscow State University, Moscow, Russia

    Georgy V. Maximov, Sergei V. Kotelevtsev & Sergei N. Orlov

  4. Centre de recherche, CRCHUM—Technopôle Angus, 2901 rue Rachel Est, Montreal, Quebec, H1W 4A4, Canada

    Sergei N. Orlov

Authors
  1. Svetlana V. Koltsova
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Georgy V. Maximov
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sergei V. Kotelevtsev
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Julie L. Lavoie
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Johanne Tremblay
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ryszard Grygorczyk
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Pavel Hamet
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Sergei N. Orlov
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sergei N. Orlov.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Koltsova, S.V., Maximov, G.V., Kotelevtsev, S.V. et al. Myogenic tone in mouse mesenteric arteries: evidence for P2Y receptor-mediated, Na+, K+, 2Cl− cotransport-dependent signaling. Purinergic Signalling 5, 343–349 (2009). https://doi.org/10.1007/s11302-009-9160-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11302-009-9160-4

Keywords

Search

Navigation