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Activation of κ-opioid receptor by U50,488H improves vascular dysfunction in streptozotocin-induced diabetic rats.

Zhou X, Wang D, Zhang Y, Zhang J, Xiang D, Wang H - BMC Endocr Disord (2015)

Bottom Line: U50,488H treatment resulted in reduction in ANG II, sICAM-1, IL-6 and IL-8 levels and elevation in NO levels, while these effects were abolished by nor-BNI treatment.Further more, eNOS phosphorylation was increased, and NF-κB p65 translocation was decreased after U50,488H treatment.Our study demonstrated that U50,488H may have therapeutic effects on diabetic vascular dysfunction by improving endothelial dysfunction and attenuating chronic inflammation, which may be dependent on phosphorylation of eNOS and downstream inhibition of NF-кB.

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, 710032, China. zhouxuanxuan2007@126.com.

ABSTRACT

Background: Evidence suggests that activation of κ-opioid receptor (KOR) by U50,488H exhibits potential cardiovascular protective properties. However, the effects of U50,488H on vascular dysfunction in diabetes mellitus (DM) are still not clear. The present study was designed to investigate the effects of U50,488H on vascular dysfunction in diabetic rats and explore the underlying mechanisms involved.

Methods: Rats were randomly divided into control, DM, DM + vehicle, DM + U50,488H and DM + nor-binaltorphimine (nor-BNI) groups. Streptozotocin injection was used to induce DM. Weight, blood glucose, blood pressure and plasma insulin for each group were measured. Arterial functions were assessed with isolated vessels mounted for isometric tension recordings. Angiotensin II (ANG II), soluble intercellular adhesion molecule-1 (sICAM-1), interleukin (IL)-6 and IL-8 levels were measured by ELISA, and endothelial nitric oxide synthase (eNOS) phosphorylation and NF-κB p65 translocation were measured by Western blot.

Results: Activation of KOR by U50,488H reduced the enhanced contractility of aortas to KCl and noradrenaline and increased acetylcholine-induced vascular relaxation, which could also protect the aortal ultrastructure in DM. U50,488H treatment resulted in reduction in ANG II, sICAM-1, IL-6 and IL-8 levels and elevation in NO levels, while these effects were abolished by nor-BNI treatment. Further more, eNOS phosphorylation was increased, and NF-κB p65 translocation was decreased after U50,488H treatment.

Conclusions: Our study demonstrated that U50,488H may have therapeutic effects on diabetic vascular dysfunction by improving endothelial dysfunction and attenuating chronic inflammation, which may be dependent on phosphorylation of eNOS and downstream inhibition of NF-кB.

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Related in: MedlinePlus

U50,488H suppressed DM-induced inflammatory response through NF-кB inhibition. ELISA analysis showed significant increases in serum levels of IL-6 (A), IL-8 (B), and sICAM-1 (C) in DM rats as compared with the CON group, and U50,488H treatment prevented these increases. (D) NF-κB p65 translocation was increased in DM rats as compared with the CON group, which was markedly attenuated by U50,488H treatment. *P < 0.05 vs. CON group, #P < 0.05 vs. DM group. (n = 5).
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Fig5: U50,488H suppressed DM-induced inflammatory response through NF-кB inhibition. ELISA analysis showed significant increases in serum levels of IL-6 (A), IL-8 (B), and sICAM-1 (C) in DM rats as compared with the CON group, and U50,488H treatment prevented these increases. (D) NF-κB p65 translocation was increased in DM rats as compared with the CON group, which was markedly attenuated by U50,488H treatment. *P < 0.05 vs. CON group, #P < 0.05 vs. DM group. (n = 5).

Mentions: To determine whether U50,488H inhibited the DM-induced inflammatory response in rats, pro-inflammatory cytokines and adhesion molecule levels were measured. As shown in Figure 5A-C, concentrations of IL-6, IL-8 and sICAM-1 increased markedly in the DM group compared with the CON group. Treatment with U50,488H inhibited DM-induced IL-6, IL-8 and sICAM-1 production but did not restore them to the normal levels, while nor-BNI treatment further increased IL-6, IL-8 and sICAM-1 production.Figure 5


Activation of κ-opioid receptor by U50,488H improves vascular dysfunction in streptozotocin-induced diabetic rats.

Zhou X, Wang D, Zhang Y, Zhang J, Xiang D, Wang H - BMC Endocr Disord (2015)

U50,488H suppressed DM-induced inflammatory response through NF-кB inhibition. ELISA analysis showed significant increases in serum levels of IL-6 (A), IL-8 (B), and sICAM-1 (C) in DM rats as compared with the CON group, and U50,488H treatment prevented these increases. (D) NF-κB p65 translocation was increased in DM rats as compared with the CON group, which was markedly attenuated by U50,488H treatment. *P < 0.05 vs. CON group, #P < 0.05 vs. DM group. (n = 5).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4355970&req=5

Fig5: U50,488H suppressed DM-induced inflammatory response through NF-кB inhibition. ELISA analysis showed significant increases in serum levels of IL-6 (A), IL-8 (B), and sICAM-1 (C) in DM rats as compared with the CON group, and U50,488H treatment prevented these increases. (D) NF-κB p65 translocation was increased in DM rats as compared with the CON group, which was markedly attenuated by U50,488H treatment. *P < 0.05 vs. CON group, #P < 0.05 vs. DM group. (n = 5).
Mentions: To determine whether U50,488H inhibited the DM-induced inflammatory response in rats, pro-inflammatory cytokines and adhesion molecule levels were measured. As shown in Figure 5A-C, concentrations of IL-6, IL-8 and sICAM-1 increased markedly in the DM group compared with the CON group. Treatment with U50,488H inhibited DM-induced IL-6, IL-8 and sICAM-1 production but did not restore them to the normal levels, while nor-BNI treatment further increased IL-6, IL-8 and sICAM-1 production.Figure 5

Bottom Line: U50,488H treatment resulted in reduction in ANG II, sICAM-1, IL-6 and IL-8 levels and elevation in NO levels, while these effects were abolished by nor-BNI treatment.Further more, eNOS phosphorylation was increased, and NF-κB p65 translocation was decreased after U50,488H treatment.Our study demonstrated that U50,488H may have therapeutic effects on diabetic vascular dysfunction by improving endothelial dysfunction and attenuating chronic inflammation, which may be dependent on phosphorylation of eNOS and downstream inhibition of NF-кB.

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, 710032, China. zhouxuanxuan2007@126.com.

ABSTRACT

Background: Evidence suggests that activation of κ-opioid receptor (KOR) by U50,488H exhibits potential cardiovascular protective properties. However, the effects of U50,488H on vascular dysfunction in diabetes mellitus (DM) are still not clear. The present study was designed to investigate the effects of U50,488H on vascular dysfunction in diabetic rats and explore the underlying mechanisms involved.

Methods: Rats were randomly divided into control, DM, DM + vehicle, DM + U50,488H and DM + nor-binaltorphimine (nor-BNI) groups. Streptozotocin injection was used to induce DM. Weight, blood glucose, blood pressure and plasma insulin for each group were measured. Arterial functions were assessed with isolated vessels mounted for isometric tension recordings. Angiotensin II (ANG II), soluble intercellular adhesion molecule-1 (sICAM-1), interleukin (IL)-6 and IL-8 levels were measured by ELISA, and endothelial nitric oxide synthase (eNOS) phosphorylation and NF-κB p65 translocation were measured by Western blot.

Results: Activation of KOR by U50,488H reduced the enhanced contractility of aortas to KCl and noradrenaline and increased acetylcholine-induced vascular relaxation, which could also protect the aortal ultrastructure in DM. U50,488H treatment resulted in reduction in ANG II, sICAM-1, IL-6 and IL-8 levels and elevation in NO levels, while these effects were abolished by nor-BNI treatment. Further more, eNOS phosphorylation was increased, and NF-κB p65 translocation was decreased after U50,488H treatment.

Conclusions: Our study demonstrated that U50,488H may have therapeutic effects on diabetic vascular dysfunction by improving endothelial dysfunction and attenuating chronic inflammation, which may be dependent on phosphorylation of eNOS and downstream inhibition of NF-кB.

Show MeSH
Related in: MedlinePlus