Research Article
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The effect of P2X1 receptor on vascular responses in the diabetic rat model

Year 2023, Volume: 9 Issue: 3, 277 - 283, 01.09.2023
https://doi.org/10.53394/akd.1034657

Abstract

ABSTRACT
Objective: Although it is known that there are changes in the vascular purinergic system in diabetes, it is unknown whether P2X1-mediated vascular responses are affected. In this study, we aimed to investigate the vascular responses mediated by P2X1 receptor activation in streptozotocin-induced diabetes model.
Method: Animals were divided into two groups as diabetes and control. Diabetes was induced by 65 mg/kg single dose of streptozotocin. After 12 weeks, second branches of the mesenteric artery were isolated and placed into the wire myograph to evaluate the vascular responses to ATP and P2X1 receptor agonist. Vascular responses were also examined in the presence of endothelial nitric oxide synthase, cyclooxygenase or K+ channel inhibitors, to determine the possible mechanism/s of relaxation responses.
Results: In diabetes group relaxation responses to ATP and P2X1 receptor agonist were lower compared to control group. Vascular relaxation responses to P2X1 receptor agonist were significantly decreased in both groups in the presence of endothelial nitric oxide synthase inhibitor. Cyclooxygenase inhibitor and K+ channels inhibitors significantly blocked vascular relaxation responses in diabetes group but not in control animals.
Conclusion: The results of this study revealed that vascular P2X1 receptor-mediated relaxation responses are decreased in diabetes in diabetes and the pathways mediating these responses were changed.

Supporting Institution

Akdeniz Üniversitesi BAP Birimi

Project Number

TYL-2017-2676

Thanks

This study was supported by the Akdeniz University Research Projects Unit (Project cod. TYL-2017-2676)

References

  • REFERENCES 1. Burnstock G. Purinergic Signaling in the Cardiovascular System. Circ Res 2017;120(1):207-28.
  • 2. Ralevic V. P2X receptors in the cardiovascular system and their potential as therapeutic targets in disease. Curr Med Chem 2015;22(7):851-65.
  • 3. Burnstock G, Ralevic V. Purinergic signaling and blood vessels in health and disease. Pharmacol Rev 2014;66(1):102-92.
  • 4. Kunapuli SP, Daniel JL. P2 receptor subtypes in the cardiovascular system. Biochem J 1998;336 ( Pt 3):513-23.
  • 5. North RA. Molecular physiology of P2X receptors. Physiol Rev 2002;82(4):1013-67.
  • 6. Vulchanova L, Arvidsson U, Riedl M, Wang J, Buell G, Surprenant A, North RA, Elde R. Differential distribution of two ATP-gated channels (P2X receptors) determined by immunocytochemistry. Proc Natl Acad Sci USA 1996;93(15):8063-7.
  • 7. Hansen MA, Dutton JL, Balcar VJ, Barden JA, Bennett MR. P2X (purinergic) receptor distributions in rat blood vessels. J Auton Nerv Syst 1999;75(2-3):147-55.
  • 8. Yamamoto K, Sokabe T, Matsumoto T, Yoshimura K, Shibata M, Ohura N, Fukuda T, Sato T, Sekine K, Kato S, Isshiki M, Fujita T, Kobayashi M, Kawamura K, Masuda H, Kamiya A, Ando J. Impaired flow-dependent control of vascular tone and remodeling in P2X4-deficient mice. Nat Med 2006;12(1):133-7.
  • 9. Glass R, Townsend-Nicholson A, Burnstock G. P2 receptors in the thymus: expression of P2X and P2Y receptors in adult rats, an immunohistochemical and in situ hybridisation study. Cell Tissue Res 2000;300(2):295-306.
  • 10. Ray FR, Huang W, Slater M, Barden JA. Purinergic receptor distribution in endothelial cells in blood vessels: a basis for selection of coronary artery grafts. Atherosclerosis 2002;162(1):55-61.
  • 11. Harrington LS, Mitchell JA. Novel role for P2X receptor activation in endothelium-dependent vasodilation. Br J Pharmacol 2004;143(5):611-7.
  • 12. Kreft E, Kowalski R, Jankowski M, Szczepanska-Konkel M. Renal vasculature reactivity to agonist of P2X7 receptor is increased in streptozotocin-induced diabetes. Pharmacol Rep 2016;68(1):71-4.
  • 13. Ishida K, Matsumoto T, Taguchi K, Kamata K, Kobayashi T. Mechanisms underlying reduced P2Y(1) -receptor-mediated relaxation in superior mesenteric arteries from long-term streptozotocin-induced diabetic rats. Acta Physiol (Oxf) 2013;207(1):130-41.
  • 14. Sathanoori R, Sward K, Olde B, Erlinge D. The ATP Receptors P2X7 and P2X4 Modulate High Glucose and Palmitate-Induced Inflammatory Responses in Endothelial Cells. PloS One 2015;10(5):e0125111.
  • 15. Vareniuk I, Pavlov IA, Obrosova IG. Inducible nitric oxide synthase gene deficiency counteracts multiple manifestations of peripheral neuropathy in a streptozotocin-induced mouse model of diabetes. Diabetologia 2008;51(11):2126-33.
  • 16. Zheng L, Du Y, Miller C, Gubitosi-Klug RA, Kern TS, Ball S, Berkowitz BA. Critical role of inducible nitric oxide synthase in degeneration of retinal capillaries in mice with streptozotocin-induced diabetes. Diabetologia 2007;50(9):1987-96.
  • 17. Sartoretto JL, Oliveira MA, Nigro D, Carvalho MH, Tostes RC, Fortes ZB. Constrictor responses to noradrenaline, hemodynamic profile, and superoxide levels measured by hydroethidine oxidation in diabetic rats. Biol Pharm Bull 2007;30(10):1938-42.
  • 18. Guan Z, Singletary ST, Cha H, Van Beusecum JP, Cook AK, Pollock JS, Pollock DM, Inscho EW. Pentosan polysulfate preserves renal microvascular P2X1 receptor reactivity and autoregulatory behavior in DOCA-salt hypertensive rats. Am J Physiol Renal Physiol 2016;310(6):F456-65.
  • 19. Harrington LS, Evans RJ, Wray J, Norling L, Swales KE, Vial C, Ali F, Carrier MJ, Mitchell JA. Purinergic 2X1 receptors mediate endothelial dependent vasodilation to ATP. Mol Pharmacol 2007;72(5):1132-6.
  • 20. Mayhan WG. Effect of diabetes mellitus on response of the basilar artery to activation of ATP-sensitive potassium channels. Brain Res 1994;636(1):35-9.
  • 21. van den Oever IA, Raterman HG, Nurmohamed MT, Simsek S. Endothelial dysfunction, inflammation, and apoptosis in diabetes mellitus. Mediators Inflamm 2010;2010:792393.
  • 22. Jansson PA. Endothelial dysfunction in insulin resistance and type 2 diabetes. J Intern Med 2007;262(2):173-83.
  • 23. Polovina MM, Potpara TS. Endothelial dysfunction in metabolic and vascular disorders. Postgrad Med 2014;126(2):38-53.
  • 24. Wallace A, Knight GE, Cowen T, Burnstock G. Changes in purinergic signalling in developing and ageing rat tail artery: importance for temperature control. Neuropharmacology 2006;50(2):191-208.
  • 25. Mayhan WG, Mayhan JF, Sun H, Patel KP. In vivo properties of potassium channels in cerebral blood vessels during diabetes mellitus. Microcirculation 2004;11(7):605-13.
  • 26. Menzies RI, Booth JWR, Mullins JJ, Bailey MA, Tam FWK, Norman JT, Unwin RJ. Hyperglycemia-induced Renal P2X7 Receptor Activation Enhances Diabetes-related Injury. EBioMedicine 2017;19:73-83.

Diyabetik sıçan modelinde damar yanıtları üzerine P2X1 reseptörünün etkisi

Year 2023, Volume: 9 Issue: 3, 277 - 283, 01.09.2023
https://doi.org/10.53394/akd.1034657

Abstract

ÖZ
Amaç: Diyabette vasküler pürinerjik sinyalizasyonun değiştiği bilinmesine rağmen, P2X1 aracılı vasküler yanıtların etkilenip etkilenmediği bilinmemektedir. Bu çalışmada, streptozotosin ile oluşturulan diyabetik sıçan modelinde P2X1 reseptör aracılı vasküler yanıtları incelemeyi amaçladık.
Yöntem: Hayvanlar kontrol ve diyabet olmak üzere iki gruba ayrıldı. Diyabet grubundaki sıçanlara 65 mg/kg streptozotosin, intraperitoneal yolla tek doz uygulandı. 12 hafta sonra mezenter arterin ikinci dalı alınarak, ATP ve P2X1 reseptör agonistine cevaben oluşan damar yanıtları, telli miyograf düzeneği kullanılarak değerlendirildi. Vasküler gevşeme yanıtlarına aracılık edebilecek olası mekanizma/ların açığa çılarılması amacıyla, vasküler yanıtlar aynı zamanda endotelial nitrik oksit sentaz, siklooksijenaz ve K+ kanal inhibitörlerinin varlığında da incelendi.
Bulgular: Diyabet grubunda ATP ve P2X1 reseptörüne verilen gevşeme yanıtları kontrol grubuna kıyasla önemli düzeyde düşük bulundu. P2X1 reseptör agonistine cevaben oluşan gevşeme yanıtları her iki grupta endotelial nitrik oksit sentaz inhibitörü varlığında önemli derecede azalma gösterdi. Siklooksijenaz inhibitörü ve K+ kanal inhibitörleri ise diyabet grubunda vasküler gevşeme yanıtlarını önemli düzeyde baskılarken, kontrol grubunda etkili bulunmadı.
Sonuç: Bu çalışmanın sonuçları, diyabette vasküler P2X1 reseptör aracılı gevşeme yanıtlarının azaldığını ve bu yanıtlara aracılık eden yolakların değiştiğini ortaya koymuştur.

Project Number

TYL-2017-2676

References

  • REFERENCES 1. Burnstock G. Purinergic Signaling in the Cardiovascular System. Circ Res 2017;120(1):207-28.
  • 2. Ralevic V. P2X receptors in the cardiovascular system and their potential as therapeutic targets in disease. Curr Med Chem 2015;22(7):851-65.
  • 3. Burnstock G, Ralevic V. Purinergic signaling and blood vessels in health and disease. Pharmacol Rev 2014;66(1):102-92.
  • 4. Kunapuli SP, Daniel JL. P2 receptor subtypes in the cardiovascular system. Biochem J 1998;336 ( Pt 3):513-23.
  • 5. North RA. Molecular physiology of P2X receptors. Physiol Rev 2002;82(4):1013-67.
  • 6. Vulchanova L, Arvidsson U, Riedl M, Wang J, Buell G, Surprenant A, North RA, Elde R. Differential distribution of two ATP-gated channels (P2X receptors) determined by immunocytochemistry. Proc Natl Acad Sci USA 1996;93(15):8063-7.
  • 7. Hansen MA, Dutton JL, Balcar VJ, Barden JA, Bennett MR. P2X (purinergic) receptor distributions in rat blood vessels. J Auton Nerv Syst 1999;75(2-3):147-55.
  • 8. Yamamoto K, Sokabe T, Matsumoto T, Yoshimura K, Shibata M, Ohura N, Fukuda T, Sato T, Sekine K, Kato S, Isshiki M, Fujita T, Kobayashi M, Kawamura K, Masuda H, Kamiya A, Ando J. Impaired flow-dependent control of vascular tone and remodeling in P2X4-deficient mice. Nat Med 2006;12(1):133-7.
  • 9. Glass R, Townsend-Nicholson A, Burnstock G. P2 receptors in the thymus: expression of P2X and P2Y receptors in adult rats, an immunohistochemical and in situ hybridisation study. Cell Tissue Res 2000;300(2):295-306.
  • 10. Ray FR, Huang W, Slater M, Barden JA. Purinergic receptor distribution in endothelial cells in blood vessels: a basis for selection of coronary artery grafts. Atherosclerosis 2002;162(1):55-61.
  • 11. Harrington LS, Mitchell JA. Novel role for P2X receptor activation in endothelium-dependent vasodilation. Br J Pharmacol 2004;143(5):611-7.
  • 12. Kreft E, Kowalski R, Jankowski M, Szczepanska-Konkel M. Renal vasculature reactivity to agonist of P2X7 receptor is increased in streptozotocin-induced diabetes. Pharmacol Rep 2016;68(1):71-4.
  • 13. Ishida K, Matsumoto T, Taguchi K, Kamata K, Kobayashi T. Mechanisms underlying reduced P2Y(1) -receptor-mediated relaxation in superior mesenteric arteries from long-term streptozotocin-induced diabetic rats. Acta Physiol (Oxf) 2013;207(1):130-41.
  • 14. Sathanoori R, Sward K, Olde B, Erlinge D. The ATP Receptors P2X7 and P2X4 Modulate High Glucose and Palmitate-Induced Inflammatory Responses in Endothelial Cells. PloS One 2015;10(5):e0125111.
  • 15. Vareniuk I, Pavlov IA, Obrosova IG. Inducible nitric oxide synthase gene deficiency counteracts multiple manifestations of peripheral neuropathy in a streptozotocin-induced mouse model of diabetes. Diabetologia 2008;51(11):2126-33.
  • 16. Zheng L, Du Y, Miller C, Gubitosi-Klug RA, Kern TS, Ball S, Berkowitz BA. Critical role of inducible nitric oxide synthase in degeneration of retinal capillaries in mice with streptozotocin-induced diabetes. Diabetologia 2007;50(9):1987-96.
  • 17. Sartoretto JL, Oliveira MA, Nigro D, Carvalho MH, Tostes RC, Fortes ZB. Constrictor responses to noradrenaline, hemodynamic profile, and superoxide levels measured by hydroethidine oxidation in diabetic rats. Biol Pharm Bull 2007;30(10):1938-42.
  • 18. Guan Z, Singletary ST, Cha H, Van Beusecum JP, Cook AK, Pollock JS, Pollock DM, Inscho EW. Pentosan polysulfate preserves renal microvascular P2X1 receptor reactivity and autoregulatory behavior in DOCA-salt hypertensive rats. Am J Physiol Renal Physiol 2016;310(6):F456-65.
  • 19. Harrington LS, Evans RJ, Wray J, Norling L, Swales KE, Vial C, Ali F, Carrier MJ, Mitchell JA. Purinergic 2X1 receptors mediate endothelial dependent vasodilation to ATP. Mol Pharmacol 2007;72(5):1132-6.
  • 20. Mayhan WG. Effect of diabetes mellitus on response of the basilar artery to activation of ATP-sensitive potassium channels. Brain Res 1994;636(1):35-9.
  • 21. van den Oever IA, Raterman HG, Nurmohamed MT, Simsek S. Endothelial dysfunction, inflammation, and apoptosis in diabetes mellitus. Mediators Inflamm 2010;2010:792393.
  • 22. Jansson PA. Endothelial dysfunction in insulin resistance and type 2 diabetes. J Intern Med 2007;262(2):173-83.
  • 23. Polovina MM, Potpara TS. Endothelial dysfunction in metabolic and vascular disorders. Postgrad Med 2014;126(2):38-53.
  • 24. Wallace A, Knight GE, Cowen T, Burnstock G. Changes in purinergic signalling in developing and ageing rat tail artery: importance for temperature control. Neuropharmacology 2006;50(2):191-208.
  • 25. Mayhan WG, Mayhan JF, Sun H, Patel KP. In vivo properties of potassium channels in cerebral blood vessels during diabetes mellitus. Microcirculation 2004;11(7):605-13.
  • 26. Menzies RI, Booth JWR, Mullins JJ, Bailey MA, Tam FWK, Norman JT, Unwin RJ. Hyperglycemia-induced Renal P2X7 Receptor Activation Enhances Diabetes-related Injury. EBioMedicine 2017;19:73-83.
There are 26 citations in total.

Details

Primary Language English
Subjects Clinical Sciences
Journal Section Research Article
Authors

Günel Abdullayeva This is me 0000-0003-1898-790X

Nur Özen This is me 0000-0002-2332-3449

Pınar Ülker This is me 0000-0003-1772-5641

Filiz Basralı 0000-0002-6692-7779

Project Number TYL-2017-2676
Early Pub Date August 30, 2023
Publication Date September 1, 2023
Submission Date December 14, 2021
Published in Issue Year 2023 Volume: 9 Issue: 3

Cite

APA Abdullayeva, G., Özen, N., Ülker, P., Basralı, F. (2023). The effect of P2X1 receptor on vascular responses in the diabetic rat model. Akdeniz Tıp Dergisi, 9(3), 277-283. https://doi.org/10.53394/akd.1034657