Mechanisms Underlying Pioglitazone-Mediated Relaxation in Isolated Blood Vessel
Pioglitazone is a widely used anti-type 2 diabetic drug. Beside its insulin-sensitizing effects, pioglitazone exerts preventive roles against ischemic heart disease. Since one possible explanation is anti-hypertensive action, we examined effects of pioglitazone on contractility of isolated blood ves...
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| Format: | Article |
| Language: | English |
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Elsevier
2008-01-01
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| Series: | Journal of Pharmacological Sciences |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1347861319313325 |
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| author | Hidemi Nomura Hideyuki Yamawaki Masashi Mukohda Muneyoshi Okada Yukio Hara |
| author_facet | Hidemi Nomura Hideyuki Yamawaki Masashi Mukohda Muneyoshi Okada Yukio Hara |
| author_sort | Hidemi Nomura |
| collection | DOAJ |
| description | Pioglitazone is a widely used anti-type 2 diabetic drug. Beside its insulin-sensitizing effects, pioglitazone exerts preventive roles against ischemic heart disease. Since one possible explanation is anti-hypertensive action, we examined effects of pioglitazone on contractility of isolated blood vessel. Endothelium-intact [End (+)] or -removed [End (−)] rat aorta is isolated and isometric tension is recorded. In both End (+) and End (−) aorta, pretreatment with pioglitazone (3 –10 μM, 30 min) inhibited noradrenaline (NA) (1 nM –1 μM)-induced contraction. In NA (100 nM)-pre-contracted aorta, pioglitazone (1 –10 μM) directly induced a relaxation. The relaxant effect is higher in End (−) aorta than in End (+) aorta. In End (+) aorta, NG-nitro-L-arginine methyl ester (100 μM) significantly inhibited the relaxation. In End (−) aorta, neither indomethacin nor cimetidine affected the relaxation, but tetraethylammonium (10 mM) inhibited it. Furthermore, the relaxation was significantly inhibited by a voltage-dependent K+ (KV)-channel blocker, 4-aminopyridine (1 mM), or an inward rectifying K+ (KIR)-channel blocker, BaCl2 (1 mM). GW9662 (2 μM), a blocker of peroxisome proliferator-activated receptor (PPAR)-γ was ineffective against the relaxation. The present study demonstrated that pioglitazone causes PPAR-γ–independent relaxation. While endothelium-dependent relaxation is mediated via nitric oxide, the endothelium-independent one is responsible for smooth muscle K+ (KV, KIR)-channel opening. Keywords:: diabetes, endothelium, smooth muscle, nitric oxide, potassium channel |
| first_indexed | 2024-12-10T13:12:11Z |
| format | Article |
| id | doaj.art-a895e5dc1d9544518255f2c0aada2d1f |
| institution | Directory Open Access Journal |
| issn | 1347-8613 |
| language | English |
| last_indexed | 2024-12-10T13:12:11Z |
| publishDate | 2008-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Pharmacological Sciences |
| spelling | doaj.art-a895e5dc1d9544518255f2c0aada2d1f2022-12-22T01:47:38ZengElsevierJournal of Pharmacological Sciences1347-86132008-01-011083258265Mechanisms Underlying Pioglitazone-Mediated Relaxation in Isolated Blood VesselHidemi Nomura0Hideyuki Yamawaki1Masashi Mukohda2Muneyoshi Okada3Yukio Hara4Department of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Towada, Aomori 034-8628, JapanDepartment of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Towada, Aomori 034-8628, Japan; Corresponding author. yamawaki@vmas.kitasato-u.ac.jpDepartment of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Towada, Aomori 034-8628, JapanDepartment of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Towada, Aomori 034-8628, JapanDepartment of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Towada, Aomori 034-8628, JapanPioglitazone is a widely used anti-type 2 diabetic drug. Beside its insulin-sensitizing effects, pioglitazone exerts preventive roles against ischemic heart disease. Since one possible explanation is anti-hypertensive action, we examined effects of pioglitazone on contractility of isolated blood vessel. Endothelium-intact [End (+)] or -removed [End (−)] rat aorta is isolated and isometric tension is recorded. In both End (+) and End (−) aorta, pretreatment with pioglitazone (3 –10 μM, 30 min) inhibited noradrenaline (NA) (1 nM –1 μM)-induced contraction. In NA (100 nM)-pre-contracted aorta, pioglitazone (1 –10 μM) directly induced a relaxation. The relaxant effect is higher in End (−) aorta than in End (+) aorta. In End (+) aorta, NG-nitro-L-arginine methyl ester (100 μM) significantly inhibited the relaxation. In End (−) aorta, neither indomethacin nor cimetidine affected the relaxation, but tetraethylammonium (10 mM) inhibited it. Furthermore, the relaxation was significantly inhibited by a voltage-dependent K+ (KV)-channel blocker, 4-aminopyridine (1 mM), or an inward rectifying K+ (KIR)-channel blocker, BaCl2 (1 mM). GW9662 (2 μM), a blocker of peroxisome proliferator-activated receptor (PPAR)-γ was ineffective against the relaxation. The present study demonstrated that pioglitazone causes PPAR-γ–independent relaxation. While endothelium-dependent relaxation is mediated via nitric oxide, the endothelium-independent one is responsible for smooth muscle K+ (KV, KIR)-channel opening. Keywords:: diabetes, endothelium, smooth muscle, nitric oxide, potassium channelhttp://www.sciencedirect.com/science/article/pii/S1347861319313325 |
| spellingShingle | Hidemi Nomura Hideyuki Yamawaki Masashi Mukohda Muneyoshi Okada Yukio Hara Mechanisms Underlying Pioglitazone-Mediated Relaxation in Isolated Blood Vessel Journal of Pharmacological Sciences |
| title | Mechanisms Underlying Pioglitazone-Mediated Relaxation in Isolated Blood Vessel |
| title_full | Mechanisms Underlying Pioglitazone-Mediated Relaxation in Isolated Blood Vessel |
| title_fullStr | Mechanisms Underlying Pioglitazone-Mediated Relaxation in Isolated Blood Vessel |
| title_full_unstemmed | Mechanisms Underlying Pioglitazone-Mediated Relaxation in Isolated Blood Vessel |
| title_short | Mechanisms Underlying Pioglitazone-Mediated Relaxation in Isolated Blood Vessel |
| title_sort | mechanisms underlying pioglitazone mediated relaxation in isolated blood vessel |
| url | http://www.sciencedirect.com/science/article/pii/S1347861319313325 |
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