High glucose effects on endothelium-dependent vasorelaxation in isolated thoracic aorta of spontaneously hypertensive rats - 25/09/20
Résumé |
Introduction |
There is an increasing evidence regarding the relationship between metabolic syndrome components and cardiovascular complications leading to vascular disorders and type 2 diabetes. Cardio-metabolic risk factors have been reported to promote the development of endothelial dysfunction. Nevertheless, the direct impact of these factors on the mechanisms underlying endothelial dysfunction remain poorly understood.
Objective |
The aim was to identify the impact of hyperglycaemia on endothelial function in spontaneously hypertensive rat (SHR). For this we investigated the direct effect of high glucose short-term incubation on endothelium-dependent relaxation on isolated thoracic aorta.
Method |
Thirty-eight SHR males, 12-weeks old (weighting on average 330g) were used for this study. Thoracic aortae were isolated and cut into rings. Aortic rings were precontracted with 1μM phenylephrine and cumulative concentration-response curves (CCRCs) to acetylcholine (1nM to 0.1mM) and sodium nitroprusside (10nM to 10μM) were performed in aortic rings exposed during two hours to a normal (11mM) or to a high glucose concentration (25mM). A non-linear mixed effects model was used to compare the CCRCs parameters (pD2 and Emax). A significant level of P=0.05 was used for statistical comparison.
Results |
In phenylephrine-precontracted rings, acetylcholine produced a concentration-dependent relaxation (Emax=87.06±3.04% and pD2 was 6.99±0.06; n=20). Incubation of aortic rings in high glucose for 2hours led to an impairment of the acetylcholine-induced relaxation (pD2=6.57±0.08 and Emax=79.95±4.19%; P<0.001 vs. control; n=20). Pretreatment of aortic rings with apocynin (30μM), a NADPH oxidase inhibitor, or indomethacin (1μM), a non-selective COX inhibitor, increased the maximal effect of acetylcholine-induced relaxation (Emax=101.06±5.20% and Emax=97,98±4.70% after apocynin and indomethacin respectively, P<0.01 vs. control) in control group. The vasorelaxation was also improved in the high glucose group (Emax=97.96±4.70% and 102.34±5.05% respectively, P<0.001 vs. high glucose group after apocynin or indomethacin respectively), with an increase of acetylcholine sensitivity by indomethacin (pD2=7.23±0.10; P<0.001 vs. high glucose group after indomethacin).
Conclusion |
We found that short-term incubation with high glucose led to an impairment of endothelium-dependent relaxation of SHR thoracic aorta. This impairment could involve NADPH oxidase and COX products, that may be responsible for a decrease of nitric oxide bioavailability and its vasorelaxant activity.
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Vol 12 - N° 2-4
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