ADMA and oxidative stress are responsible for endothelial dysfunction in hyperhomocyst(e)inemia : effects of L-arginine and B vitamins
Hyperhomocyst(e)inemia is a risk factor for atherosclerotic vascular disease, and it is associated with endothelial dysfunction. Mechanisms responsible for endothelial dysfunction in hyperhomocyst(e)inemia may involve impaired bioavailability of NO, possibly secondary to accumulation of the endogeno...
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| Veröffentlicht in: | Cardiovascular research 2003, Vol.57 (1), p.244-252 |
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| creator | SYDOW, Karsten SCHWEDHELM, Edzard ARAKAWA, Naoshi BODE-BÖGER, Stefanie M TSIKAS, Dimitrios HORNIG, Burkhard FRÖLICH, Jürgen C BÖGER, Rainer H |
| description | Hyperhomocyst(e)inemia is a risk factor for atherosclerotic vascular disease, and it is associated with endothelial dysfunction. Mechanisms responsible for endothelial dysfunction in hyperhomocyst(e)inemia may involve impaired bioavailability of NO, possibly secondary to accumulation of the endogenous NO synthase inhibitor asymmetric dimethylarginine (ADMA) and increased oxidative stress. We investigated whether oral treatment with B vitamins or L-arginine normalizes endothelium-dependent, flow-dependent vasodilation (FDD) in patients with peripheral arterial occlusive disease (PAOD) and hyperhomocyst(e)inemia.
27 patients with PAOD and hyperhomocyst(e)inemia were assigned to oral treatment with combined B vitamins (folate, 10 mg; vitamin B-12, 200 microg; vitamin B-6, 20 mg/day), L-arginine (24 g/day) or placebo, for 8 weeks in a double-blind fashion. FDD was determined by high-resolution ultrasound in the radial artery.
Vitamin B supplementation significantly lowered plasma homocyst(e)ine concentration from 15.8+/-1.8 to 8.7+/-1.1 micromol/l (P |
| doi_str_mv | 10.1016/S0008-6363(02)00617-X |
| format | Article |
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27 patients with PAOD and hyperhomocyst(e)inemia were assigned to oral treatment with combined B vitamins (folate, 10 mg; vitamin B-12, 200 microg; vitamin B-6, 20 mg/day), L-arginine (24 g/day) or placebo, for 8 weeks in a double-blind fashion. FDD was determined by high-resolution ultrasound in the radial artery.
Vitamin B supplementation significantly lowered plasma homocyst(e)ine concentration from 15.8+/-1.8 to 8.7+/-1.1 micromol/l (P<0.01). However, B vitamins had no significant effect on FDD (baseline, 7.8+/-0.7%, B vitamins, 8.3+/-0.9%, placebo 8.9+/-0.7%; P=n.s.). In contrast, L-arginine treatment did not affect homocyst(e)ine levels, but significantly improved FDD (10.2+/-0.2%), probably by antagonizing the impact of elevated ADMA concentration (3.8+/-0.3 micromol/l) and reducing the oxidative stress by lowering urinary 8-iso-prostaglandin F(2alpha) (baseline, 76.3+/-7.1 vs. 62.7+/-8.3 pmol/mmol creatinine after 8 weeks).
Oral supplementation with combined B vitamins during 8 weeks does not improve endothelium-dependent vasodilation in PAOD patients with hyperhomocyst(e)inemia, whereas L-arginine significantly improved endothelial function in these patients. Thus, accumulation of ADMA and increased oxidative stress may underlie endothelial dysfunction under hyperhomocyst(e)inemic conditions. These findings may have importance for evaluation of homocyst(e)ine-lowering therapy.</description><identifier>ISSN: 0008-6363</identifier><identifier>EISSN: 1755-3245</identifier><identifier>DOI: 10.1016/S0008-6363(02)00617-X</identifier><identifier>PMID: 12504835</identifier><identifier>CODEN: CVREAU</identifier><language>eng</language><publisher>Oxford: Oxford University Press</publisher><subject>Aged ; Analysis of Variance ; Arginine - analogs & derivatives ; Arginine - blood ; Arginine - therapeutic use ; Arterial Occlusive Diseases - blood ; Arterial Occlusive Diseases - drug therapy ; Atherosclerosis (general aspects, experimental research) ; Biological and medical sciences ; Blood and lymphatic vessels ; Cardiology. Vascular system ; Double-Blind Method ; Female ; Folic Acid - blood ; Folic Acid - therapeutic use ; Humans ; Hyperhomocysteinemia - blood ; Hyperhomocysteinemia - drug therapy ; Male ; Medical sciences ; Middle Aged ; Nitric Oxide Synthase - antagonists & inhibitors ; Oxidative Stress ; Peripheral Vascular Diseases - blood ; Peripheral Vascular Diseases - drug therapy ; Vitamin B 12 - blood ; Vitamin B 12 - therapeutic use ; Vitamin B 6 - blood ; Vitamin B 6 - therapeutic use ; Vitamins - therapeutic use</subject><ispartof>Cardiovascular research, 2003, Vol.57 (1), p.244-252</ispartof><rights>2003 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,4022,27922,27923,27924</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=14430341$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12504835$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>SYDOW, Karsten</creatorcontrib><creatorcontrib>SCHWEDHELM, Edzard</creatorcontrib><creatorcontrib>ARAKAWA, Naoshi</creatorcontrib><creatorcontrib>BODE-BÖGER, Stefanie M</creatorcontrib><creatorcontrib>TSIKAS, Dimitrios</creatorcontrib><creatorcontrib>HORNIG, Burkhard</creatorcontrib><creatorcontrib>FRÖLICH, Jürgen C</creatorcontrib><creatorcontrib>BÖGER, Rainer H</creatorcontrib><title>ADMA and oxidative stress are responsible for endothelial dysfunction in hyperhomocyst(e)inemia : effects of L-arginine and B vitamins</title><title>Cardiovascular research</title><addtitle>Cardiovasc Res</addtitle><description>Hyperhomocyst(e)inemia is a risk factor for atherosclerotic vascular disease, and it is associated with endothelial dysfunction. Mechanisms responsible for endothelial dysfunction in hyperhomocyst(e)inemia may involve impaired bioavailability of NO, possibly secondary to accumulation of the endogenous NO synthase inhibitor asymmetric dimethylarginine (ADMA) and increased oxidative stress. We investigated whether oral treatment with B vitamins or L-arginine normalizes endothelium-dependent, flow-dependent vasodilation (FDD) in patients with peripheral arterial occlusive disease (PAOD) and hyperhomocyst(e)inemia.
27 patients with PAOD and hyperhomocyst(e)inemia were assigned to oral treatment with combined B vitamins (folate, 10 mg; vitamin B-12, 200 microg; vitamin B-6, 20 mg/day), L-arginine (24 g/day) or placebo, for 8 weeks in a double-blind fashion. FDD was determined by high-resolution ultrasound in the radial artery.
Vitamin B supplementation significantly lowered plasma homocyst(e)ine concentration from 15.8+/-1.8 to 8.7+/-1.1 micromol/l (P<0.01). However, B vitamins had no significant effect on FDD (baseline, 7.8+/-0.7%, B vitamins, 8.3+/-0.9%, placebo 8.9+/-0.7%; P=n.s.). In contrast, L-arginine treatment did not affect homocyst(e)ine levels, but significantly improved FDD (10.2+/-0.2%), probably by antagonizing the impact of elevated ADMA concentration (3.8+/-0.3 micromol/l) and reducing the oxidative stress by lowering urinary 8-iso-prostaglandin F(2alpha) (baseline, 76.3+/-7.1 vs. 62.7+/-8.3 pmol/mmol creatinine after 8 weeks).
Oral supplementation with combined B vitamins during 8 weeks does not improve endothelium-dependent vasodilation in PAOD patients with hyperhomocyst(e)inemia, whereas L-arginine significantly improved endothelial function in these patients. Thus, accumulation of ADMA and increased oxidative stress may underlie endothelial dysfunction under hyperhomocyst(e)inemic conditions. These findings may have importance for evaluation of homocyst(e)ine-lowering therapy.</description><subject>Aged</subject><subject>Analysis of Variance</subject><subject>Arginine - analogs & derivatives</subject><subject>Arginine - blood</subject><subject>Arginine - therapeutic use</subject><subject>Arterial Occlusive Diseases - blood</subject><subject>Arterial Occlusive Diseases - drug therapy</subject><subject>Atherosclerosis (general aspects, experimental research)</subject><subject>Biological and medical sciences</subject><subject>Blood and lymphatic vessels</subject><subject>Cardiology. Vascular system</subject><subject>Double-Blind Method</subject><subject>Female</subject><subject>Folic Acid - blood</subject><subject>Folic Acid - therapeutic use</subject><subject>Humans</subject><subject>Hyperhomocysteinemia - blood</subject><subject>Hyperhomocysteinemia - drug therapy</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Nitric Oxide Synthase - antagonists & inhibitors</subject><subject>Oxidative Stress</subject><subject>Peripheral Vascular Diseases - blood</subject><subject>Peripheral Vascular Diseases - drug therapy</subject><subject>Vitamin B 12 - blood</subject><subject>Vitamin B 12 - therapeutic use</subject><subject>Vitamin B 6 - blood</subject><subject>Vitamin B 6 - therapeutic use</subject><subject>Vitamins - therapeutic use</subject><issn>0008-6363</issn><issn>1755-3245</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpF0MlOwzAQBmALgaAsjwDyBVQOAa9ZuJUdqYgDHLhVTjymRokdbBfRF-C5iaDAaWb0f5qRBqF9Sk4oofnpIyGkzHKe8zFhx4TktMie19CIFlJmnAm5jkZ_ZAttx_g6jFIWYhNtUSaJKLkcoc_J5f0EK6ex_7BaJfsOOKYAMWIVAA9N7120dQvY-IDBaZ_m0FrVYr2MZuGaZL3D1uH5socw951vljGN4dg66KzCZxiMgSZF7A2eZiq8WDdE3yfP8btNqrMu7qINo9oIe6u6g56ur54ubrPpw83dxWSa9YwXKRO1amShDDeUSA2ClpxCaThjOi8k1VUDVNdlbgpaaaZFJXOda62MqSsOwHfQ0c_aPvi3BcQ062xsoG2VA7-Is4JVvGJMDPBgBRd1B3rWB9upsJz9Pm4AhyugYqNaE5RrbPx3QnDCBeVfpjOANQ</recordid><startdate>2003</startdate><enddate>2003</enddate><creator>SYDOW, Karsten</creator><creator>SCHWEDHELM, Edzard</creator><creator>ARAKAWA, Naoshi</creator><creator>BODE-BÖGER, Stefanie M</creator><creator>TSIKAS, Dimitrios</creator><creator>HORNIG, Burkhard</creator><creator>FRÖLICH, Jürgen C</creator><creator>BÖGER, Rainer H</creator><general>Oxford University Press</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>2003</creationdate><title>ADMA and oxidative stress are responsible for endothelial dysfunction in hyperhomocyst(e)inemia : effects of L-arginine and B vitamins</title><author>SYDOW, Karsten ; SCHWEDHELM, Edzard ; ARAKAWA, Naoshi ; BODE-BÖGER, Stefanie M ; TSIKAS, Dimitrios ; HORNIG, Burkhard ; FRÖLICH, Jürgen C ; BÖGER, Rainer H</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p237t-4bac57af3f105de41831e8f322d6751d9ce1db86f719d2d4956d6ddaffb93ee3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Aged</topic><topic>Analysis of Variance</topic><topic>Arginine - analogs & derivatives</topic><topic>Arginine - blood</topic><topic>Arginine - therapeutic use</topic><topic>Arterial Occlusive Diseases - blood</topic><topic>Arterial Occlusive Diseases - drug therapy</topic><topic>Atherosclerosis (general aspects, experimental research)</topic><topic>Biological and medical sciences</topic><topic>Blood and lymphatic vessels</topic><topic>Cardiology. Vascular system</topic><topic>Double-Blind Method</topic><topic>Female</topic><topic>Folic Acid - blood</topic><topic>Folic Acid - therapeutic use</topic><topic>Humans</topic><topic>Hyperhomocysteinemia - blood</topic><topic>Hyperhomocysteinemia - drug therapy</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Nitric Oxide Synthase - antagonists & inhibitors</topic><topic>Oxidative Stress</topic><topic>Peripheral Vascular Diseases - blood</topic><topic>Peripheral Vascular Diseases - drug therapy</topic><topic>Vitamin B 12 - blood</topic><topic>Vitamin B 12 - therapeutic use</topic><topic>Vitamin B 6 - blood</topic><topic>Vitamin B 6 - therapeutic use</topic><topic>Vitamins - therapeutic use</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>SYDOW, Karsten</creatorcontrib><creatorcontrib>SCHWEDHELM, Edzard</creatorcontrib><creatorcontrib>ARAKAWA, Naoshi</creatorcontrib><creatorcontrib>BODE-BÖGER, Stefanie M</creatorcontrib><creatorcontrib>TSIKAS, Dimitrios</creatorcontrib><creatorcontrib>HORNIG, Burkhard</creatorcontrib><creatorcontrib>FRÖLICH, Jürgen C</creatorcontrib><creatorcontrib>BÖGER, Rainer H</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>Cardiovascular research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>SYDOW, Karsten</au><au>SCHWEDHELM, Edzard</au><au>ARAKAWA, Naoshi</au><au>BODE-BÖGER, Stefanie M</au><au>TSIKAS, Dimitrios</au><au>HORNIG, Burkhard</au><au>FRÖLICH, Jürgen C</au><au>BÖGER, Rainer H</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>ADMA and oxidative stress are responsible for endothelial dysfunction in hyperhomocyst(e)inemia : effects of L-arginine and B vitamins</atitle><jtitle>Cardiovascular research</jtitle><addtitle>Cardiovasc Res</addtitle><date>2003</date><risdate>2003</risdate><volume>57</volume><issue>1</issue><spage>244</spage><epage>252</epage><pages>244-252</pages><issn>0008-6363</issn><eissn>1755-3245</eissn><coden>CVREAU</coden><abstract>Hyperhomocyst(e)inemia is a risk factor for atherosclerotic vascular disease, and it is associated with endothelial dysfunction. Mechanisms responsible for endothelial dysfunction in hyperhomocyst(e)inemia may involve impaired bioavailability of NO, possibly secondary to accumulation of the endogenous NO synthase inhibitor asymmetric dimethylarginine (ADMA) and increased oxidative stress. We investigated whether oral treatment with B vitamins or L-arginine normalizes endothelium-dependent, flow-dependent vasodilation (FDD) in patients with peripheral arterial occlusive disease (PAOD) and hyperhomocyst(e)inemia.
27 patients with PAOD and hyperhomocyst(e)inemia were assigned to oral treatment with combined B vitamins (folate, 10 mg; vitamin B-12, 200 microg; vitamin B-6, 20 mg/day), L-arginine (24 g/day) or placebo, for 8 weeks in a double-blind fashion. FDD was determined by high-resolution ultrasound in the radial artery.
Vitamin B supplementation significantly lowered plasma homocyst(e)ine concentration from 15.8+/-1.8 to 8.7+/-1.1 micromol/l (P<0.01). However, B vitamins had no significant effect on FDD (baseline, 7.8+/-0.7%, B vitamins, 8.3+/-0.9%, placebo 8.9+/-0.7%; P=n.s.). In contrast, L-arginine treatment did not affect homocyst(e)ine levels, but significantly improved FDD (10.2+/-0.2%), probably by antagonizing the impact of elevated ADMA concentration (3.8+/-0.3 micromol/l) and reducing the oxidative stress by lowering urinary 8-iso-prostaglandin F(2alpha) (baseline, 76.3+/-7.1 vs. 62.7+/-8.3 pmol/mmol creatinine after 8 weeks).
Oral supplementation with combined B vitamins during 8 weeks does not improve endothelium-dependent vasodilation in PAOD patients with hyperhomocyst(e)inemia, whereas L-arginine significantly improved endothelial function in these patients. Thus, accumulation of ADMA and increased oxidative stress may underlie endothelial dysfunction under hyperhomocyst(e)inemic conditions. These findings may have importance for evaluation of homocyst(e)ine-lowering therapy.</abstract><cop>Oxford</cop><pub>Oxford University Press</pub><pmid>12504835</pmid><doi>10.1016/S0008-6363(02)00617-X</doi><tpages>9</tpages></addata></record> |
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| source | MEDLINE; Oxford University Press Journals All Titles (1996-Current); EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Aged Analysis of Variance Arginine - analogs & derivatives Arginine - blood Arginine - therapeutic use Arterial Occlusive Diseases - blood Arterial Occlusive Diseases - drug therapy Atherosclerosis (general aspects, experimental research) Biological and medical sciences Blood and lymphatic vessels Cardiology. Vascular system Double-Blind Method Female Folic Acid - blood Folic Acid - therapeutic use Humans Hyperhomocysteinemia - blood Hyperhomocysteinemia - drug therapy Male Medical sciences Middle Aged Nitric Oxide Synthase - antagonists & inhibitors Oxidative Stress Peripheral Vascular Diseases - blood Peripheral Vascular Diseases - drug therapy Vitamin B 12 - blood Vitamin B 12 - therapeutic use Vitamin B 6 - blood Vitamin B 6 - therapeutic use Vitamins - therapeutic use |
| title | ADMA and oxidative stress are responsible for endothelial dysfunction in hyperhomocyst(e)inemia : effects of L-arginine and B vitamins |
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