Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8345010 | Nitric Oxide | 2016 | 10 Pages |
Abstract
Diabetes impairs endothelium-dependent relaxations. The present study evaluated the contribution of different endothelium-dependent relaxing mechanisms to the regulation of vascular tone in subcutaneous blood vessels of humans with Type 2 diabetes mellitus. Subcutaneous arteries were isolated from tissues of healthy controls and diabetics. Vascular function was determined using wire myography. Expressions of proteins were measured by Western blotting and immunostaining. Endothelium-dependent relaxations to acetylcholine were impaired in arteries from diabetics compared to controls (P = 0.009). Acetylcholine-induced nitric oxide (NO)-mediated relaxations [in the presence of an inhibitor of cyclooxygenases (COX; indomethacin) and small and intermediate conductance calcium-activated potassium channel blockers (UCL1684 and TRAM 34, respectively)] were attenuated in arteries from diabetics compared to controls (P < 0.001). However, endothelium-dependent hyperpolarization (EDH)-type relaxations [in the presence of indomethacin and the NO synthase blocker, l-NAME] were augmented in arteries from diabetics compared to controls (P = 0.003). Endothelium-independent relaxations to sodium nitroprusside (NO donor) and salbutamol (β-adrenoceptor agonist) were preserved, but those to prostacyclin were attenuated in diabetics compared to controls (P = 0.017). In arteries of diabetics, protein expressions of endothelial NO synthase, prostacyclin synthase and prostacyclin receptors were decreased, but those of COX-2 were increased. These findings suggest that in human diabetes, the impairment of endothelium-dependent relaxations is caused by a diminished NO bioavailability; however, EDH appears to compensate, at least in part, for this dysfunction.
Keywords
PGISEDHKClT2DMeNOSCOX-2COX-1l-NG-Nitroarginine methyl esterHydrogen peroxideEndothelial dysfunctionArachidonic acidDiabetesEETType 2 diabetes mellitusendothelial nitric oxide synthaseProstacyclin synthasecyclooxygenase-1Cyclooxygenase-2Nitric oxideH2O2endothelium-dependent hyperpolarizationPyrazolePotassium chlorideProstacyclin receptor
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Authors
Siti Safiah Mokhtar, Paul M. Vanhoutte, Susan Wai Sum Leung, Mohd Imran Yusof, Wan Azman Wan Sulaiman, Arman Zaharil Mat Saad, Rapeah Suppian, Aida Hanum Ghulam Rasool,