Diyabetik sıçan modelinde damar yanıtları üzerine P2X1 reseptörünün etkisi

Öz

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.

Anahtar Kelimeler

• diyabet
• pürinerjik sinyalizasyon
• vazodilatasyon

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

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.

Keywords

• diabetes
• purinergic signaling
• vasodilatation

References

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