Methylglyoxal Accumulation in Arterial Walls Causes Vascular Contractile Dysfunction in Spontaneously Hypertensive Rats
Methylglyoxal (MGO) is a metabolite of glucose and perhaps mediates diabetes-related macrovascular complications including hypertension. In the present study, we examined if MGO accumulation affects vascular reactivity of isolated mesenteric artery from spontaneously hypertensive rats (SHR). Five-we...
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| Format: | Article |
| Language: | English |
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Elsevier
2012-01-01
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| Series: | Journal of Pharmacological Sciences |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S134786131930461X |
| _version_ | 1818301544374730752 |
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| author | Masashi Mukohda Muneyoshi Okada Yukio Hara Hideyuki Yamawaki |
| author_facet | Masashi Mukohda Muneyoshi Okada Yukio Hara Hideyuki Yamawaki |
| author_sort | Masashi Mukohda |
| collection | DOAJ |
| description | Methylglyoxal (MGO) is a metabolite of glucose and perhaps mediates diabetes-related macrovascular complications including hypertension. In the present study, we examined if MGO accumulation affects vascular reactivity of isolated mesenteric artery from spontaneously hypertensive rats (SHR). Five-week-old SHR were treated with an MGO scavenger, aminoguanidine (AG), for 5 weeks. AG partially normalized increased blood pressure in SHR. In mesenteric artery from SHR treated with AG, increased accumulation of MGO-derived advanced glycation end-products was reversed. In mesenteric artery from SHR, AG normalized impaired acetylcholine (ACh)-induced relaxation and increased angiotensin (Ang) II-induced contraction. Reactive oxygen species (ROS) production increased in SHR mesenteric artery, and acute treatment with a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) inhibitor augmented ACh-induced relaxation. Protein expression of NOX1 and Ang II type 2 receptor (AT2R) increased in SHR mesenteric artery, which was normalized by AG. Acute treatment with an AT2R blocker but not a NOX inhibitor normalized the increased Ang II-induced contraction in SHR mesenteric artery. The present results demonstrate that MGO accumulation in mesenteric artery may mediate development of hypertension in SHR at least in part via increased ROS-mediated impairment of endothelium-dependent relaxation and AT2R-mediated increased Ang II contraction. Keywords:: glucose metabolite, smooth muscle, endothelium, vascular reactivity, reactive oxygen species |
| first_indexed | 2024-12-13T05:24:42Z |
| format | Article |
| id | doaj.art-e98d2f5d0da543cd9e07d9a181ef5707 |
| institution | Directory Open Access Journal |
| issn | 1347-8613 |
| language | English |
| last_indexed | 2024-12-13T05:24:42Z |
| publishDate | 2012-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Pharmacological Sciences |
| spelling | doaj.art-e98d2f5d0da543cd9e07d9a181ef57072022-12-21T23:58:13ZengElsevierJournal of Pharmacological Sciences1347-86132012-01-0112012635Methylglyoxal Accumulation in Arterial Walls Causes Vascular Contractile Dysfunction in Spontaneously Hypertensive RatsMasashi Mukohda0Muneyoshi Okada1Yukio Hara2Hideyuki Yamawaki3Laboratory 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, JapanLaboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Aomori 034-8628, Japan; Corresponding author. yamawaki@vmas.kitasato-u.ac.jpMethylglyoxal (MGO) is a metabolite of glucose and perhaps mediates diabetes-related macrovascular complications including hypertension. In the present study, we examined if MGO accumulation affects vascular reactivity of isolated mesenteric artery from spontaneously hypertensive rats (SHR). Five-week-old SHR were treated with an MGO scavenger, aminoguanidine (AG), for 5 weeks. AG partially normalized increased blood pressure in SHR. In mesenteric artery from SHR treated with AG, increased accumulation of MGO-derived advanced glycation end-products was reversed. In mesenteric artery from SHR, AG normalized impaired acetylcholine (ACh)-induced relaxation and increased angiotensin (Ang) II-induced contraction. Reactive oxygen species (ROS) production increased in SHR mesenteric artery, and acute treatment with a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) inhibitor augmented ACh-induced relaxation. Protein expression of NOX1 and Ang II type 2 receptor (AT2R) increased in SHR mesenteric artery, which was normalized by AG. Acute treatment with an AT2R blocker but not a NOX inhibitor normalized the increased Ang II-induced contraction in SHR mesenteric artery. The present results demonstrate that MGO accumulation in mesenteric artery may mediate development of hypertension in SHR at least in part via increased ROS-mediated impairment of endothelium-dependent relaxation and AT2R-mediated increased Ang II contraction. Keywords:: glucose metabolite, smooth muscle, endothelium, vascular reactivity, reactive oxygen specieshttp://www.sciencedirect.com/science/article/pii/S134786131930461X |
| spellingShingle | Masashi Mukohda Muneyoshi Okada Yukio Hara Hideyuki Yamawaki Methylglyoxal Accumulation in Arterial Walls Causes Vascular Contractile Dysfunction in Spontaneously Hypertensive Rats Journal of Pharmacological Sciences |
| title | Methylglyoxal Accumulation in Arterial Walls Causes Vascular Contractile Dysfunction in Spontaneously Hypertensive Rats |
| title_full | Methylglyoxal Accumulation in Arterial Walls Causes Vascular Contractile Dysfunction in Spontaneously Hypertensive Rats |
| title_fullStr | Methylglyoxal Accumulation in Arterial Walls Causes Vascular Contractile Dysfunction in Spontaneously Hypertensive Rats |
| title_full_unstemmed | Methylglyoxal Accumulation in Arterial Walls Causes Vascular Contractile Dysfunction in Spontaneously Hypertensive Rats |
| title_short | Methylglyoxal Accumulation in Arterial Walls Causes Vascular Contractile Dysfunction in Spontaneously Hypertensive Rats |
| title_sort | methylglyoxal accumulation in arterial walls causes vascular contractile dysfunction in spontaneously hypertensive rats |
| url | http://www.sciencedirect.com/science/article/pii/S134786131930461X |
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