Curcumin ameliorates high glucose-induced acute vascular endothelial dysfunction in rat thoracic aorta.
1. The aims of the present study were to explore the protective effect of curcumin against the acute vascular endothelial dysfunction induced by high glucose and to investigate the possible role of heme oxygenase (HO)-1 in this protective action. 2. Thoracic aortic rings, with or without endothelium, obtained from male Sprague-Dawley rats were mounted in an organ bath. Isometric contraction of the rings was recorded. After completion of the organ bath studies, rings were homogenized and centrifuged (30,000 g, 4 degrees C, 15 min) and HO activity was determined in the supernatant. 3. After 2 h incubation of aortic rings in the presence of high glucose (44 mmol/L), the relaxation evoked by acetylcholine (3 x 10(-8) to 3 x 10(-5) mol/L) was significantly decreased only in rings with an intact endothelium. When rings were coincubated in the presence of curcumin (10(-13) to 10(-11) mol/L) and high glucose, curcumin reversed the vasodilator dysfunction induced by high glucose dose dependently. 4. Curcumin (10(-11) mol/L) increased HO activity in the aortic rings compared with activity in control rings (63.1 +/- 3.6 vs control 43.2 +/- 2.9 pmol/mg per h, respectively; P < 0.01). Protoporphyrin IX zinc (10(-6) mol/L), an inhibitor of HO-1, offset the protective effects of curcumin. In addition, the non-selective guanylate cyclase (GC) inhibitor methylene blue (10(-6) mol/L) completely abolished the protective effects of curcumin. 5. In conclusion, the results of the present study show that curcumin alleviates the acute endothelium-dependent vasodilator dysfunction induced by high glucose in rat aortic rings. Increased HO-1 activity and stimulation of GC may be involved in the protective effects of curcumin.
Fang
Xiao-Dong
XD
National Education Base for Basic Medical Sciences, Zhejiang University School of Medicine, Hangzhou, China.
Yang
Fan
F
Zhu
Li
L
Shen
Yue-Liang
YL
Wang
Lin-Lin
LL
Chen
Ying-Ying
YY
D000109:Acetylcholine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D003474:Curcumin / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D005947:Glucose / Q000009:adverse effects*; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D051547:Heme Oxygenase-1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D009126:Muscle Relaxation / Q000187:drug effects* / Q000502:physiology; D011524:Protoporphyrins / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014664:Vasodilation / Q000187:drug effects
D002316:Cardiotonic Agents; D011524:Protoporphyrins; C017803:zinc protoporphyrin; D051547:Heme Oxygenase-1; D006162:Guanylate Cyclase; D003474:Curcumin; D005947:Glucose; D000109:Acetylcholine; D008751:Methylene Blue