Methylglyoxal Inhibits Smooth Muscle Contraction in Isolated Blood Vessels
Methylglyoxal (MGO) is a metabolite of glucose. In addition to evidence that increased plasma MGO level is associated with diabetic vascular complications, recent studies demonstrated that MGO accumulated in vascular tissues of hypertensive animals. We hypothesized that MGO could directly affect vas...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2009-01-01
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| Series: | Journal of Pharmacological Sciences |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1347861319312861 |
| _version_ | 1818193087276515328 |
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| author | Masashi Mukohda Hideyuki Yamawaki Hidemi Nomura Muneyoshi Okada Yukio Hara |
| author_facet | Masashi Mukohda Hideyuki Yamawaki Hidemi Nomura Muneyoshi Okada Yukio Hara |
| author_sort | Masashi Mukohda |
| collection | DOAJ |
| description | Methylglyoxal (MGO) is a metabolite of glucose. In addition to evidence that increased plasma MGO level is associated with diabetic vascular complications, recent studies demonstrated that MGO accumulated in vascular tissues of hypertensive animals. We hypothesized that MGO could directly affect vascular reactivity. To test the hypothesis, we examined effects of MGO on contraction of isolated blood vessels. Treatment of endothelium-denuded rat aorta with MGO (420 μM, 30 min) shifted the concentration–response curve for noradrenaline (NA: 1nM–1 μM) to the right. The inhibitory effect was concentration-dependent (MGO: 42 – 420 μM). Indomethacin (10 μM) and cimetidine (30 μM) could not prevent the inhibitory effect of MGO. However, a non-selective K+-channel inhibitor, tetramethylammonium (10 mM), prevented it. Glibenclamide (3 μM), an ATP-sensitive K+-channel inhibitor or apamin (1 μM), a small conductance Ca2+-activated K+-channel inhibitor was ineffective, but iberiotoxin (100 nM), a large conductance Ca2+-activated K+ (BKCa)-channel inhibitor significantly prevented the effect of MGO. MGO (420 μM, 30 min) also inhibited the NA (1 nM – 1 μM)-induced contraction in mesenteric artery. The present results indicate that MGO has an inhibitory effect on contractility of isolated blood vessel, which is mediated via opening smooth muscle BKCa channel. Keywords:: glucose metabolite, vascular smooth muscle, contraction, potassium channel |
| first_indexed | 2024-12-12T00:40:49Z |
| format | Article |
| id | doaj.art-38e1fb608948451992dd0b9f7baee9fe |
| institution | Directory Open Access Journal |
| issn | 1347-8613 |
| language | English |
| last_indexed | 2024-12-12T00:40:49Z |
| publishDate | 2009-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Pharmacological Sciences |
| spelling | doaj.art-38e1fb608948451992dd0b9f7baee9fe2022-12-22T00:44:15ZengElsevierJournal of Pharmacological Sciences1347-86132009-01-011092305310Methylglyoxal Inhibits Smooth Muscle Contraction in Isolated Blood VesselsMasashi Mukohda0Hideyuki Yamawaki1Hidemi Nomura2Muneyoshi Okada3Yukio Hara4Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Aomori 034-8628, JapanLaboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Aomori 034-8628, Japan; Corresponding author. yamawaki@vmas.kitasato-u.ac.jpLaboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Aomori 034-8628, JapanLaboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Aomori 034-8628, JapanLaboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Aomori 034-8628, JapanMethylglyoxal (MGO) is a metabolite of glucose. In addition to evidence that increased plasma MGO level is associated with diabetic vascular complications, recent studies demonstrated that MGO accumulated in vascular tissues of hypertensive animals. We hypothesized that MGO could directly affect vascular reactivity. To test the hypothesis, we examined effects of MGO on contraction of isolated blood vessels. Treatment of endothelium-denuded rat aorta with MGO (420 μM, 30 min) shifted the concentration–response curve for noradrenaline (NA: 1nM–1 μM) to the right. The inhibitory effect was concentration-dependent (MGO: 42 – 420 μM). Indomethacin (10 μM) and cimetidine (30 μM) could not prevent the inhibitory effect of MGO. However, a non-selective K+-channel inhibitor, tetramethylammonium (10 mM), prevented it. Glibenclamide (3 μM), an ATP-sensitive K+-channel inhibitor or apamin (1 μM), a small conductance Ca2+-activated K+-channel inhibitor was ineffective, but iberiotoxin (100 nM), a large conductance Ca2+-activated K+ (BKCa)-channel inhibitor significantly prevented the effect of MGO. MGO (420 μM, 30 min) also inhibited the NA (1 nM – 1 μM)-induced contraction in mesenteric artery. The present results indicate that MGO has an inhibitory effect on contractility of isolated blood vessel, which is mediated via opening smooth muscle BKCa channel. Keywords:: glucose metabolite, vascular smooth muscle, contraction, potassium channelhttp://www.sciencedirect.com/science/article/pii/S1347861319312861 |
| spellingShingle | Masashi Mukohda Hideyuki Yamawaki Hidemi Nomura Muneyoshi Okada Yukio Hara Methylglyoxal Inhibits Smooth Muscle Contraction in Isolated Blood Vessels Journal of Pharmacological Sciences |
| title | Methylglyoxal Inhibits Smooth Muscle Contraction in Isolated Blood Vessels |
| title_full | Methylglyoxal Inhibits Smooth Muscle Contraction in Isolated Blood Vessels |
| title_fullStr | Methylglyoxal Inhibits Smooth Muscle Contraction in Isolated Blood Vessels |
| title_full_unstemmed | Methylglyoxal Inhibits Smooth Muscle Contraction in Isolated Blood Vessels |
| title_short | Methylglyoxal Inhibits Smooth Muscle Contraction in Isolated Blood Vessels |
| title_sort | methylglyoxal inhibits smooth muscle contraction in isolated blood vessels |
| url | http://www.sciencedirect.com/science/article/pii/S1347861319312861 |
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