Effects of Atorvastatin, Amlodipine, and Their Combination on Vascular Dysfunction in Insulin-Resistant Rats
Abstract.: Deficiency of tetrahydrobiopterin (BH4) in the vascular tissue contributes to endothelial dysfunction through reduced eNOS activity and increased superoxide anion (O2−) generation in the insulin-resistant state. We investigated the effects of atorvastatin, a 3-hydroxyl-3-methylglutaryl co...
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| Format: | Article |
| Language: | English |
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Elsevier
2014-01-01
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| Series: | Journal of Pharmacological Sciences |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S134786131930221X |
| _version_ | 1818248862179000320 |
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| author | Tomio Okamura Masashi Tawa Ayman Geddawy Takashi Shimosato Hirotaka Iwasaki Haruo Shintaku Yuichi Yoshida Masahiro Masada Kazuya Shinozaki Takeshi Imamura |
| author_facet | Tomio Okamura Masashi Tawa Ayman Geddawy Takashi Shimosato Hirotaka Iwasaki Haruo Shintaku Yuichi Yoshida Masahiro Masada Kazuya Shinozaki Takeshi Imamura |
| author_sort | Tomio Okamura |
| collection | DOAJ |
| description | Abstract.: Deficiency of tetrahydrobiopterin (BH4) in the vascular tissue contributes to endothelial dysfunction through reduced eNOS activity and increased superoxide anion (O2−) generation in the insulin-resistant state. We investigated the effects of atorvastatin, a 3-hydroxyl-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitor; amlodipine, a calcium antagonist; and their combination on blood pressure, arterial relaxation and contraction, and vascular oxidative stress in aortas of high fructose–fed rats. Oral administration of atorvastatin for 8 weeks did not significantly lower blood pressure, but normalized angiotensin II–induced vasoconstriction and endothelial function in the fructose-fed rats. Atorvastatin treatment of fructose-fed rats increased vascular BH4 content, which was associated with an increase in endothelial NO synthase activity as well as a reduction in endothelial O2− production. On the other hand, administration of amlodipine did not affect the angiotensin II–induced vasoconstriction and endothelial function, but normalized the elevated blood pressure in the fructose-fed rats. The combined treatment did not show synergistic but additive beneficial effects. The present study suggests that combined therapy of HMG-CoA reductase inhibitors and calcium antagonists prevents functional vascular disorders in the insulin-resistant state, possibly resulting in the protection against or delay of development of hypertension, vascular dysfunction in diabetes, and thereafter atherosclerosis. Keywords:: 3-hydroxyl-3-methylglutaryl coenzyme A reductase inhibitor, calcium antagonist, nitric oxide, tetrahydrobiopterin, insulin resistance |
| first_indexed | 2024-12-12T15:27:20Z |
| format | Article |
| id | doaj.art-f1159cd23700444cb3ec2a36531b9a19 |
| institution | Directory Open Access Journal |
| issn | 1347-8613 |
| language | English |
| last_indexed | 2024-12-12T15:27:20Z |
| publishDate | 2014-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Pharmacological Sciences |
| spelling | doaj.art-f1159cd23700444cb3ec2a36531b9a192022-12-22T00:20:12ZengElsevierJournal of Pharmacological Sciences1347-86132014-01-0112417685Effects of Atorvastatin, Amlodipine, and Their Combination on Vascular Dysfunction in Insulin-Resistant RatsTomio Okamura0Masashi Tawa1Ayman Geddawy2Takashi Shimosato3Hirotaka Iwasaki4Haruo Shintaku5Yuichi Yoshida6Masahiro Masada7Kazuya Shinozaki8Takeshi Imamura9Department of Pharmacology, Shiga University of Medical Science, Otsu 520-2192, Japan; Corresponding author. okamura@belle.shiga-med.ac.jpDepartment of Pharmacology, Shiga University of Medical Science, Otsu 520-2192, JapanDepartment of Pharmacology, Shiga University of Medical Science, Otsu 520-2192, Japan; Present address: Department of Pharmacology, Faculty of Medicine, Minia University, EgyptDepartment of Pharmacology, Shiga University of Medical Science, Otsu 520-2192, JapanDepartment of Pharmacology, Shiga University of Medical Science, Otsu 520-2192, JapanDepartment of Pediatrics, Osaka City University Graduate School of Medicine, Osaka 545-8585, JapanLaboratory of Biochemistry, Faculty of Horticulture, Chiba University, Matsudo 271-8510, JapanLaboratory of Biochemistry, Faculty of Horticulture, Chiba University, Matsudo 271-8510, JapanDepartment of Pharmacology, Shiga University of Medical Science, Otsu 520-2192, JapanDepartment of Pharmacology, Shiga University of Medical Science, Otsu 520-2192, JapanAbstract.: Deficiency of tetrahydrobiopterin (BH4) in the vascular tissue contributes to endothelial dysfunction through reduced eNOS activity and increased superoxide anion (O2−) generation in the insulin-resistant state. We investigated the effects of atorvastatin, a 3-hydroxyl-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitor; amlodipine, a calcium antagonist; and their combination on blood pressure, arterial relaxation and contraction, and vascular oxidative stress in aortas of high fructose–fed rats. Oral administration of atorvastatin for 8 weeks did not significantly lower blood pressure, but normalized angiotensin II–induced vasoconstriction and endothelial function in the fructose-fed rats. Atorvastatin treatment of fructose-fed rats increased vascular BH4 content, which was associated with an increase in endothelial NO synthase activity as well as a reduction in endothelial O2− production. On the other hand, administration of amlodipine did not affect the angiotensin II–induced vasoconstriction and endothelial function, but normalized the elevated blood pressure in the fructose-fed rats. The combined treatment did not show synergistic but additive beneficial effects. The present study suggests that combined therapy of HMG-CoA reductase inhibitors and calcium antagonists prevents functional vascular disorders in the insulin-resistant state, possibly resulting in the protection against or delay of development of hypertension, vascular dysfunction in diabetes, and thereafter atherosclerosis. Keywords:: 3-hydroxyl-3-methylglutaryl coenzyme A reductase inhibitor, calcium antagonist, nitric oxide, tetrahydrobiopterin, insulin resistancehttp://www.sciencedirect.com/science/article/pii/S134786131930221X |
| spellingShingle | Tomio Okamura Masashi Tawa Ayman Geddawy Takashi Shimosato Hirotaka Iwasaki Haruo Shintaku Yuichi Yoshida Masahiro Masada Kazuya Shinozaki Takeshi Imamura Effects of Atorvastatin, Amlodipine, and Their Combination on Vascular Dysfunction in Insulin-Resistant Rats Journal of Pharmacological Sciences |
| title | Effects of Atorvastatin, Amlodipine, and Their Combination on Vascular Dysfunction in Insulin-Resistant Rats |
| title_full | Effects of Atorvastatin, Amlodipine, and Their Combination on Vascular Dysfunction in Insulin-Resistant Rats |
| title_fullStr | Effects of Atorvastatin, Amlodipine, and Their Combination on Vascular Dysfunction in Insulin-Resistant Rats |
| title_full_unstemmed | Effects of Atorvastatin, Amlodipine, and Their Combination on Vascular Dysfunction in Insulin-Resistant Rats |
| title_short | Effects of Atorvastatin, Amlodipine, and Their Combination on Vascular Dysfunction in Insulin-Resistant Rats |
| title_sort | effects of atorvastatin amlodipine and their combination on vascular dysfunction in insulin resistant rats |
| url | http://www.sciencedirect.com/science/article/pii/S134786131930221X |
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