Malfunction of Vascular Control in Lifestyle-Related Diseases: Mechanisms Underlying Endothelial Dysfunction in the Insulin-Resistant State
It is tempting to speculate that increased vasoconstriction and loss of endothelium-dependent vasodilation might be etiological factors of elevated blood pressure in the insulin-resistant state. Vascular contraction induced by angiotensin II and the expression of NAD(P)H oxidase were increased in th...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2004-01-01
|
| Series: | Journal of Pharmacological Sciences |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1347861319323175 |
| _version_ | 1818991625678880768 |
|---|---|
| author | Kazuya Shinozaki Kazuhide Ayajiki Atsunori Kashiwagi Masahiro Masada Tomio Okamura |
| author_facet | Kazuya Shinozaki Kazuhide Ayajiki Atsunori Kashiwagi Masahiro Masada Tomio Okamura |
| author_sort | Kazuya Shinozaki |
| collection | DOAJ |
| description | It is tempting to speculate that increased vasoconstriction and loss of endothelium-dependent vasodilation might be etiological factors of elevated blood pressure in the insulin-resistant state. Vascular contraction induced by angiotensin II and the expression of NAD(P)H oxidase were increased in the aorta of insulin-resistant mice. In addition, both angiotensin II type 1 receptor expression and superoxide anion production were up-regulated in these mice. Another mechanism for imparing endothelial function is the uncoupling of endothelial nitric oxide synthase (eNOS). It has become clear from studies on the aorta of insulin-resistant rat that insulin resistance may be a pathogenic factor for endothelial dysfunction through impaired eNOS activity and increased oxidative breakdown of NO (nitric oxide) due to an enhanced formation of superoxide anion (NO/superoxide anion imbalance), which are caused by relative deficiency of tetrahydrobiopterin, a cofactor of NOS, in vascular endothelial cells. Supplementation of tetrahydrobiopterin restored endothelial function and relieved oxidative tissue damage through activation of eNOS in those rats. These results indicate that generation of superoxide anion from NAD(P)H oxidases and an uncoupled eNOS may be pathogenic factors for impaired endothelial function and hypertension in the insulin-resistant state. Keywords:: insulin resistance, endothelial dysfunction, renin-angiotensin system, nitric oxide, pteridine |
| first_indexed | 2024-12-20T20:13:15Z |
| format | Article |
| id | doaj.art-b9905142ce3148b582d43a65453062d1 |
| institution | Directory Open Access Journal |
| issn | 1347-8613 |
| language | English |
| last_indexed | 2024-12-20T20:13:15Z |
| publishDate | 2004-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Pharmacological Sciences |
| spelling | doaj.art-b9905142ce3148b582d43a65453062d12022-12-21T19:27:46ZengElsevierJournal of Pharmacological Sciences1347-86132004-01-01964401405Malfunction of Vascular Control in Lifestyle-Related Diseases: Mechanisms Underlying Endothelial Dysfunction in the Insulin-Resistant StateKazuya Shinozaki0Kazuhide Ayajiki1Atsunori Kashiwagi2Masahiro Masada3Tomio Okamura4Department of Pharmacology, Shiga University of Medical Science, Otsu, Shiga 520-2192, JapanDepartment of Pharmacology, Shiga University of Medical Science, Otsu, Shiga 520-2192, JapanDepartment of Medicine, Shiga University of Medical Science, Otsu, Shiga 520-2192, JapanLaboratory of Biochemistry, Faculty of Horticulture, Chiba University, Matsudo, Chiba 271-8510, JapanDepartment of Pharmacology, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan; Corresponding author. FAX: +81-77-548-2183 E-mail: okamura@belle.shiga-med.ac.jpIt is tempting to speculate that increased vasoconstriction and loss of endothelium-dependent vasodilation might be etiological factors of elevated blood pressure in the insulin-resistant state. Vascular contraction induced by angiotensin II and the expression of NAD(P)H oxidase were increased in the aorta of insulin-resistant mice. In addition, both angiotensin II type 1 receptor expression and superoxide anion production were up-regulated in these mice. Another mechanism for imparing endothelial function is the uncoupling of endothelial nitric oxide synthase (eNOS). It has become clear from studies on the aorta of insulin-resistant rat that insulin resistance may be a pathogenic factor for endothelial dysfunction through impaired eNOS activity and increased oxidative breakdown of NO (nitric oxide) due to an enhanced formation of superoxide anion (NO/superoxide anion imbalance), which are caused by relative deficiency of tetrahydrobiopterin, a cofactor of NOS, in vascular endothelial cells. Supplementation of tetrahydrobiopterin restored endothelial function and relieved oxidative tissue damage through activation of eNOS in those rats. These results indicate that generation of superoxide anion from NAD(P)H oxidases and an uncoupled eNOS may be pathogenic factors for impaired endothelial function and hypertension in the insulin-resistant state. Keywords:: insulin resistance, endothelial dysfunction, renin-angiotensin system, nitric oxide, pteridinehttp://www.sciencedirect.com/science/article/pii/S1347861319323175 |
| spellingShingle | Kazuya Shinozaki Kazuhide Ayajiki Atsunori Kashiwagi Masahiro Masada Tomio Okamura Malfunction of Vascular Control in Lifestyle-Related Diseases: Mechanisms Underlying Endothelial Dysfunction in the Insulin-Resistant State Journal of Pharmacological Sciences |
| title | Malfunction of Vascular Control in Lifestyle-Related Diseases: Mechanisms Underlying Endothelial Dysfunction in the Insulin-Resistant State |
| title_full | Malfunction of Vascular Control in Lifestyle-Related Diseases: Mechanisms Underlying Endothelial Dysfunction in the Insulin-Resistant State |
| title_fullStr | Malfunction of Vascular Control in Lifestyle-Related Diseases: Mechanisms Underlying Endothelial Dysfunction in the Insulin-Resistant State |
| title_full_unstemmed | Malfunction of Vascular Control in Lifestyle-Related Diseases: Mechanisms Underlying Endothelial Dysfunction in the Insulin-Resistant State |
| title_short | Malfunction of Vascular Control in Lifestyle-Related Diseases: Mechanisms Underlying Endothelial Dysfunction in the Insulin-Resistant State |
| title_sort | malfunction of vascular control in lifestyle related diseases mechanisms underlying endothelial dysfunction in the insulin resistant state |
| url | http://www.sciencedirect.com/science/article/pii/S1347861319323175 |
| work_keys_str_mv | AT kazuyashinozaki malfunctionofvascularcontrolinlifestylerelateddiseasesmechanismsunderlyingendothelialdysfunctionintheinsulinresistantstate AT kazuhideayajiki malfunctionofvascularcontrolinlifestylerelateddiseasesmechanismsunderlyingendothelialdysfunctionintheinsulinresistantstate AT atsunorikashiwagi malfunctionofvascularcontrolinlifestylerelateddiseasesmechanismsunderlyingendothelialdysfunctionintheinsulinresistantstate AT masahiromasada malfunctionofvascularcontrolinlifestylerelateddiseasesmechanismsunderlyingendothelialdysfunctionintheinsulinresistantstate AT tomiookamura malfunctionofvascularcontrolinlifestylerelateddiseasesmechanismsunderlyingendothelialdysfunctionintheinsulinresistantstate |